Abstract
Gene-finding is concerned with the identification of stretches of DNA in a genomic sequence that encode biologically active products, such as proteins or functional non-coding RNAs. This is usually the first step in the analysis of any novel piece of genomic sequence, which makes it a very important issue, as all downstream analyses depend on the results. This chapter focuses on the biological basis, computational approaches, and corresponding programs that are available for the automated identification of protein-coding genes. For prokaryotic and eukaryotic genomes, as well as the novel, multi-species sequence data originating from environmental community studies, the state of the art in automated gene finding is described.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Dong, H., Nilsson, L., Kurland, C. G. (1996) Co-variation of tRNA abundance and codon usage in Escherichia coli at different growth rates. J Mol Biol 260, 649–663.
Ikemura, T. (1981) Correlation between the abundance of Escherichia coli transfer RNAs and the occurrence of the respective codons in its protein genes: a proposal for a synonymous codon choice that is optimal for the E. coli translational system. J Mol Biol 151, 389–409.
Sharp, P. M., Bailes, E., Grocock, R. J., et al. (2005) Variation in the strength of selected codon usage bias among bacteria. Nucleic Acids Res 33, 1141–1153.
Rocha, E. P. (2004) Codon usage bias from tRNA's point of view: redundancy, specialization, and efficient decoding for translation optimization. Genome Res 14, 2279–2286.
Hooper, S. D., Berg, O. G. (2000) Gradients in nucleotide and codon usage along Escherichia coli genes. Nucleic Acids Res 28, 3517–3523.
Fickett, J. W., Tung, C. S. (1992) Assessment of protein coding measures. Nucleic Acids Res 20, 6441–6450.
Besemer, J., Lomsadze, A., Borodovsky, M. (2001) GeneMarkS: a self-training method for prediction of gene starts in microbial genomes. Implications for finding sequence motifs in regulatory regions. Nucleic Acids Res 29, 2607–2618.
Larsen, T. S., Krogh, A. (2003) EasyGene— a prokaryotic gene finder that ranks ORFs by statistical significance. BMC Bioinformatics 4, 21.
Lukashin, A. V., Borodovsky, M. (1998) GeneMark.hmm: new solutions for gene finding. Nucleic Acids Res 26, 1107–1115.
Delcher, A. L., Harmon, D., Kasif, S., et al. (1999) Improved microbial gene identification with GLIMMER. Nucleic Acids Res 27, 4636–4641.
Krause, L., McHardy, A. C., Nattkemper, T. W., et al. (2007) GISMO—gene identification using a support vector machine for ORF classification. Nucleic Acids Res 35, 540–549.
Mahony, S., McInerney, J. O., Smith, T. J., et al. (2004) Gene prediction using the Self-Organizing Map: automatic generation of multiple gene models. BMC Bioin-formatics 5, 23.
Ochman, H., Lawrence, J. G., and Groisman, E. A. (2000) Lateral gene transfer and the nature of bacterial innovation. Nature 405, 299–304.
Hayes, W. S., Borodovsky, M. (1998) How to interpret an anonymous bacterial genome: machine learning approach to gene identification. Genome Res 8, 1154–1171.
Ou, H. Y., Guo, F. B., Zhang, C. T. (2004) GS-Finder: a program to find bacterial gene start sites with a self-training method. Int J Biochem Cell Biol 36, 535–544.
Suzek, B. E., Ermolaeva, M. D., Sch-reiber, M., et al. (2001) A probabilistic method for identifying start codons in bacterial genomes. Bioinformatics 17, 1123–1130.
Tech, M., Pfeifer, N., Morgenstern, B., et al. (2005) TICO: a tool for improving predictions of prokaryotic translation initiation sites. Bioinformatics 21, 3568–3569.
Zhu, H. Q., Hu, G. Q., Ouyang, Z. Q., et al. (2004) Accuracy improvement for identifying translation initiation sites in microbial genomes. Bioinformatics 20, 3308–3317.
Shibuya, T., Rigoutsos, I. (2002) Dictionary-driven prokaryotic gene finding. Nucleic Acids Res 30, 2710–2725.
Badger, J. H., Olsen, G. J. (1999) CRITICA: coding region identification tool invoking comparative analysis. Mol Biol Evol 16, 512–524.
Frishman, D., Mironov, A., Mewes, H. W., et al. (1998) Combining diverse evidence for gene recognition in completely sequenced bacterial genomes. Nucleic Acids Res 26, 2941–2947.
McHardy, A. C., Goesmann, A., Puhler, A., et al. (2004) Development of joint application strategies for two microbial gene finders. Bioinformatics 20, 1622–1631.
Tech, M., Merkl, R. (2003) YACOP: Enhanced gene prediction obtained by a combination of existing methods. In Silico Biol 3, 441–451.
Guo, F. B., Ou, H. Y., Zhang, C. T. (2003) ZCURVE: a new system for recognizing protein-coding genes in bacterial and archaeal genomes. Nucleic Acids Res 31, 1780–1789.
Venter, J. C., Remington, K., Heidelberg, J. F., et al. (2004) Environmental genome shotgun sequencing of the Sargasso Sea. Science 304, 66–74.
Hugenholtz, P. (2002) Exploring prokaryotic diversity in the genomic era. Genome Biol 3, REVIEWS0003.
Rappe, M. S., Giovannoni, S. J. (2003) The uncultured microbial majority. Annu Rev Microbiol 57, 369–394.
Chen, K., Pachter, L. (2005) Bioinformat-ics for whole-genome shotgun sequencing of microbial communities. PLoS Comput Biol 1, 106–112.
Krause, L., Diaz, N. N., Bartels, D., et al. (2006) Finding novel genes in bacterial communities isolated from the environment. Bioinformatics 22, e281–289.
Sandberg, R., Branden, C. I., Ernberg, I., et al. (2003) Quantifying the species-specificity in genomic signatures, synonym ous codon choice, amino acid usage and G+C content. Gene 311, 35–42.
Brent, M. R., Guigo, R. (2004) Recent advances in gene structure prediction. Curr Opin Struct Biol 14, 264–272.
Mathe, C., Sagot, M. F., Schiex, T., et al. (2002) Current methods of gene prediction, their strengths and weaknesses. Nucleic Acids Res 30, 4103–4117.
Curwen, V., Eyras, E., Andrews, T. D., et al. (2004) The Ensembl automatic gene annotation system. Genome Res 14, 942–950.
Birney, E., Clamp, M., Durbin, R. (2004) GeneWise and Genomewise. Genome Res 14, 988–995.
Burge, C., Karlin, S. (1997) Prediction of complete gene structures in human genomic DNA. J Mol Biol 268, 78–94.
Slater, G. S., Birney, E. (2005) Automated generation of heuristics for biological sequence comparison. BMC Bioinformatics 6, 31.
Korf, I. (2004) Gene finding in novel genomes. BMC Bioinformatics 5, 59.
Lomsadze, A., Ter-Hovhannisyan, V., Chernoff, Y. O., et al. (2005) Gene identification in novel eukaryotic genomes by self-training algorithm. Nucleic Acids Res 33, 6494–6506.
Tenney, A. E., Brown, R. H., Vaske, C., et al. (2004) Gene prediction and verification in a compact genome with numerous small introns. Genome Res 14, 2330–2335.
Wei, C., Lamesch, P., Arumugam, M., et al. (2005) Closing in on the C. elegans ORFe-ome by cloning TWINSCAN predictions. Genome Res 15, 577–582.
Guigo, R., Reese, M. G. (2005) EGASP: collaboration through competition to find human genes. Nat Methods 2, 575–577.
Guigo, R., Flicek, P., Abril, J. F., et al. (2006) EGASP: the human ENCODE Genome Annotation Assessment Project. Genome Biol 7 Suppl 1, S21–31.
Nielsen, P., Krogh, A. (2005) Large-scale prokaryotic gene prediction and comparison to genome annotation. Bioinformatics 21, 4322–4329.
Linke, B., McHardy, A. C., Krause, L., et al. (2006) REGANOR: A gene prediction server for prokaryotic genomes and a database of high quality gene predictions for prokaryotes. Appl Bioinformatics 5, 193–198.
Skovgaard, M., Jensen, L. J., Brunak, S., et al. (2001) On the total number of genes and their length distribution in complete micro-bial genomes. Trends Genet 17, 425–428.
Osterman, A., Overbeek, R. (2003) Missing genes in metabolic pathways: a comparative genomics approach. Curr Opin Chem Biol 7, 238–251.
Acknowledgments
The author thanks Lutz Krause, Alan Grossfield, and Augustine Tsai for their comments.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
McHardy, A.C. (2008). Finding Genes in Genome Sequence. In: Keith, J.M. (eds) Bioinformatics. Methods in Molecular Biology™, vol 452. Humana Press. https://doi.org/10.1007/978-1-60327-159-2_8
Download citation
DOI: https://doi.org/10.1007/978-1-60327-159-2_8
Publisher Name: Humana Press
Print ISBN: 978-1-58829-707-5
Online ISBN: 978-1-60327-159-2
eBook Packages: Springer Protocols