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.
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Akerley BJ et al (1998) Systematic identification of essential genes by in vitro mariner mutagenesis. Proc Natl Acad Sci 95:8927–8932
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
Barrett AD, Stanberry LR (2009) Vaccines for biodefense and emerging and neglected diseases. Academic, Amsterdam
Basu MK et al (2011) ProPhylo: partial phylogenetic profiling to guide protein family construction and assignment of biological process. BMC Bioinformatics 12:1
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
Date SV, Marcotte EM (2003) Discovery of uncharacterized cellular systems by genome-wide analysis of functional linkages. Nat Biotechnol 21:1055–1062
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
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
Fleischmann RD et al (1995) Whole-genome random sequencing and assembly of Haemophilus influenzae Rd. Science 269:496–512
Forsyth R et al (2002) A genome-wide strategy for the identification of essential genes in Staphylococcus aureus. Mol Microbiol 43:1387–1400
Freilich S et al (2009) Stratification of co-evolving genomic groups using ranked phylogenetic profiles. BMC Bioinformatics 10:1
Frøkjær-Jensen C et al (2010) Targeted gene deletions in C. elegans using transposon excision. Nat Methods 7:451–453
Gaasterland T, Ragan MA (1998) Microbial genescapes: phyletic and functional patterns of ORF distribution among prokaryotes. Microb Comp Genomics 3:199–217
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
Gil R et al (2004) Determination of the core of a minimal bacterial gene set. Microbiol Mol Biol Rev 68:518–537
Grünblatt E et al (2014) Imaging genetics in obsessive-compulsive disorder: linking genetic variations to alterations in neuroimaging. Prog Neurobiol 121:114–124
Hayes F (2003) Transposon-based strategies for microbial functional genomics and proteomics. Annu Rev Genet 37:3–29
Holman AG et al (2009) Computational prediction of essential genes in an unculturable endosymbiotic bacterium, Wolbachia of Brugia malayi. BMC Microbiol 9:1
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
Huynen MA, Bork P (1998) Measuring genome evolution. Proc Natl Acad Sci 95:5849–5856
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
Ivics Z et al (2009) Transposon-mediated genome manipulation in vertebrates. Nat Methods 6:415–422
Jimenez-Ruiz E et al (2014) Advantages and disadvantages of conditional systems for characterization of essential genes in Toxoplasma gondii. Parasitology 141:1390–1398
Jordan IK et al (2002) Essential genes are more evolutionarily conserved than are nonessential genes in bacteria. Genome Res 12:962–968
Joshi PB et al (2002) Targeted gene deletion in Leishmania major identifies leishmanolysin (GP63) as a virulence factor. Mol Biochem Parasitol 120:33–40
Jothi R et al (2007) Discovering functional linkages and uncharacterized cellular pathways using phylogenetic profile comparisons: a comprehensive assessment. BMC Bioinformatics 8:1
Judson N, Mekalanos JJ (2000) Transposon-based approaches to identify essential bacterial genes. Trends Microbiol 8:521–526
Juhas M et al (2012) High confidence prediction of essential genes in Burkholderia cenocepacia. PLoS One 7:e40064
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
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
Kleckner N (1981) Transposable elements in prokaryotes. Annu Rev Genet 15:341–404
Koonin EV (2000) How many genes can make a cell: the minimal-gene-Set concept 1. Annu Rev Genomics Hum Genet 1:99–116
Langille MG et al (2013) Predictive functional profiling of microbial communities using 16S rRNA marker gene sequences. Nat Biotechnol 31:814–821
Lehoux DE et al (2001) Discovering essential and infection-related genes. Curr Opin Microbiol 4:515–519
Lin Y, Zhang RR (2011) Putative essential and core-essential genes in Mycoplasma genomes. Sci Rep 1
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
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
Mikkelsen TS et al (2005) Improving genome annotations using phylogenetic profile anomaly detection. Bioinformatics 21:464–470
O’sullivan GJ et al (2006) Potential and limitations of genetic manipulation in animals. Drug Discov Today Technol 3:173–180
Pellegrini M (2012) Using phylogenetic profiles to predict functional relationships. Bacterial Mol Netw Methods Protoc 804:167–177
Plaimas K et al (2010) Identifying essential genes in bacterial metabolic networks with machine learning methods. BMC Syst Biol 4:1
Psomopoulos FE et al (2013) Detection of genomic idiosyncrasies using fuzzy phylogenetic profiles. PLoS One 8:e52854
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
Rusmini R et al (2014) A shotgun antisense approach to the identification of novel essential genes in Pseudomonas aeruginosa. BMC Microbiol 14:1
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
Salama NR et al (2004) Global transposon mutagenesis and essential gene analysis of Helicobacter pylori. J Bacteriol 186:7926–7935
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
Sassetti CM et al (2003) Genes required for mycobacterial growth defined by high density mutagenesis. Mol Microbiol 48:77–84
Schmidt M, Oliver D (1989) SecA protein autogenously represses its own translation during normal protein secretion in Escherichia coli. J Bacteriol 171:643–649
Singh IR et al (1997) High-resolution functional mapping of a cloned gene by genetic footprinting. Proc Natl Acad Sci 94:1304–1309
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
Snitkin ES et al (2006) Comparative assessment of performance and genome dependence among phylogenetic profiling methods. BMC Bioinformatics 7:420
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
Tatusov RL et al (1997) A genomic perspective on protein families. Science 278:631–637
Touchon M et al (2009) Organised genome dynamics in the Escherichia coli species results in highly diverse adaptive paths. PLoS Genet 5:e1000344
Wong SM, Mekalanos JJ (2000) Genetic footprinting with mariner-based transposition in Pseudomonas aeruginosa. Proc Natl Acad Sci 97:10191–10196
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
Xu P et al (2011) Genome-wide essential gene identification in Streptococcus sanguinis. Sci Rep 1:125
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
Zhang Z, Ren Q (2015) Why are essential genes essential? – the essentiality of Saccharomyces genes. Microbial Cell 2:280–287
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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.
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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
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