Abstract
This book is meant to serve as an introduction to the new and very exciting field of comparative gene finding. We introduce the field in its current state, and go through the process of constructing a comparative gene finder by breaking it down into its separate building blocks. But before we can dive into the algorithmic details of such a process, we begin by giving a brief introduction to the underlying biological theory. In this chapter we introduce the basic concepts of genetics needed for this book, and define the gene finding problem we have set out to solve. We round off by giving a brief account of the historical developments of approaching the gene finding problem up to where it stands today. In the last section we split the process of building a gene finder into its smaller parts, and the rest of the book is structured in the same manner.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Alexandersson, M., Cawley, S., Pachter, L.: SLAM: cross-species gene finding and alignment with a generalized pair hidden Markov model. Genome Res. 13, 496–502 (2003)
Allen, J.E., Salzberg, S.L.: JIGSAW: integration of multiple sources of evidence for gene prediction. Bioinformatics 21, 3596–3603 (2005)
Audic, S., Claverie, J.-M.: Self-identification of protein-coding regions in microbial genomes. Proc. Natl. Acad. Sci. USA 95, 10026–10031 (1998)
Axelson-Fisk, M., Sunnerhagen, P.: Comparative genomics and gene finding in fungi. In: Sunnerhagen, P., Piskur, J. (eds.) Topics in Current Genetics: Comparative Genomics Using Fungi as Models, pp. 1–28. Springer, Berlin (2005)
Badger, J.H., Olsen, G.J.: CRITICA: coding region identification tool invoking comparative analysis. Mol. Biol. Evol. 16, 512–524 (1999)
Bafna, V., Huson, D.H.: The conserved exon method for gene finding. Int. Conf. Intell. Syst. Mol. Biol. 8, 3–12 (2000)
Batzoglou, S., Pachter, L., Mesirov, J., Berger, B., Lander, E.S.: Human and mouse gene structure: comparative analysis and application to exon prediction. Genome Res. 10, 950–958 (2000)
Beadle, G., Tatum, E.: Genetic control of biochemical reactions in Neurospora. Proc. Natl. Acad. Sci. USA 27, 499–506 (1941)
Besemer, J., Lomsadze, A., Borodovsky, M.: 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 (2001)
Biémont, C., Vieira, C.: Junk DNA as an evolutionary force. Nature 443, 521–524 (2006)
Birney, E., Clamp, M., Durbin, R.: GeneWise and GenomeWise. Genome Res. 14, 988–995 (2004)
Birney, E., Durbin, R.: Dynamite: a flexible code generating system for dynamic programming methods used in sequence comparison. Proc. Int. Conf. Intell. Syst. Mol. Biol. 5, 56–64 (1997)
Blandin, G., Durrens, P., Tekaia, F., Aigle, M., Bolotin-Fukuhara, M., Bon, E., Casarégola, S., de Montigny, J., Gaillardin, C., Lépingle, A., Llorente, B., Malpertuy, A., Neuvéglise, C., Ozier-Kalogeropoulus, O., Perrin, A., Potier, S., Souciet, J.-L., Talla, E., Toffano-Nioche, C., Wésolowski-Louvel, M., Marck, C., Dujon, B.: Genomic exploration of the hemiascomycetous yeasts: 4. The genome of Saccharomyces cerevisiae revisited. FEBS Lett. 487, 31–36 (2000)
Boeckmann, B., Bairoch, A., Apweiler, R., Blatter, M.C., Estreicher, A., Gasteiger, E., Martin, M.J., Michoud, K., O’Donovan, C., Phan, I., Pilbout, S., Schneider, M.: The SWISS-PROT protein knowledgebase and its supplement TrEMBL in 2003. Nucleic Acids Res. 31, 365–370 (2003)
Borodovsky, M., McIninch, J.: GENMARK: parallel gene recognition for both DNA strands. Comput. Chem. 17, 123–133 (1993)
Brejova, B., Brown, D.G., Li, M., Vinar, T.: ExonHunter: a comprehensive approach to gene finding. Bioinformatics 21, i57–i65 (2005)
Brunak, S., Engelbrecht, J., Knudsen, S.: Prediction of human mRNA donor and acceptor sites from the DNA sequence. J. Mol. Biol. 220, 49–65 (1991)
Burge, C., Karlin, S.: Prediction of complete gene structures in human genomic DNA. J. Mol. Biol. 268, 78–94 (1997)
Carter, D., Durbin, R.: Vertebrate gene finding from multiple-species alignments using a two-level strategy. Genome Biol. 7, S6.1–S6.12 (2006)
Cawley, S.E., Wirth, A.I., Speed, T.P.: Phat—-a gene finding program for Plasmodium falciparum. Mol. Biochem. Parasitol. 118, 167–174 (2001)
Cebrat, S., Dudek, M.R., Machiewicz, P., Kowalczuk, M., Fita, M.: Asymmetry of coding versus noncoding strand in coding sequences of different genomes. Microb. Comp. Genomics 2, 259–268 (1997)
Chatterji, S., Pachter, L.: Reference based annotation with GeneMapper. Genome Biol. 7, R29 (2006)
Chen, T., Zhang, M.Q.: Pombe: a gene-finding and exon-intron structure prediction system for fission yeast. Yeast 14, 701–710 (1998)
Cherry, J.M., Adler, C., Ball, C., Chervitz, S.A., Dwight, S.S., Hester, E.T., Jia, Y., Juvik, G., Roe, T., Schroeder, M., Weng, S., Botstein, D.: SGD: saccharomyces genome database. Nucleic Acids Res. 26, 73–79 (1998)
Claverie, J.M.: Gene number: what if there are only 30,000 human genes? Science 291, 1255–1257 (2001)
Comings, D.E.: The structure and function of chromatin. Adv. Hum. Genet. 3, 237–431 (1972)
Crick, F.: Cetnral dogma of molecular biology. Nature 227, 561–563 (1970)
Curwen, V., Eyras, E., Andrews, T.D., Clarke, L., Mongin, E., Searle, S.M.J., Clamp, M.: The ensembl automatic gene annotation system. Genome Res. 14, 942–950 (2004)
DeCaprio, D., Vinson, J.P., Pearson, M.D., Montgomery, P., Doherty, M., Galagan, J.E.: Conrad: gene prediction using conditional random fields. Genome Res. 17, 1389–1398 (2007)
Delcher, A.L., Harmon, D., Kasif, S., White, O., Salzberg, S.L.: Improved microbial gene identification with GLIMMER. Nucleic Acids Res. 27, 4636–4641 (1999)
Dong, S., Searls, D.B.: Gene structure prediction by linguistic models. Genomics 23, 540–551 (1994)
The FANTOM consortium and RIKEN genome exploration research group and genome science group (genome network project core group). Science 309, 1559–1563 (2005)
Fickett, J.W.: Recognition of protein coding regions in DNA sequences. Nucleic Acids Res. 10, 5303–5318 (1982)
Fields, C.A., Söderlund, C.A.: GM: a practical tool for automating DNA sequence analysis. Comput. Appl. Biosci. 6, 263–270 (1990)
Flicek, P., Aken, B.L., Beal, K., Ballester, B., Caccamo, M., Chen, Y., Clarke, L., Coates, G., Cunningham, F., Cutts, T., Down, T., Dyer, S.C., Eyre, T., Fitzgerald, S., Fernandez-Banet, J., Grf, S., Haider, S., Hammond, M., Holland, R., Howe, K.L., Howe, K., Johnson, N., Jenkinson, A., Khri, A., Keefe, D., Kokocinski, F., Kulesha, E., Lawson, D., Longden, I., Megy, K., Meidl, P., Overduin, B., Parker, A., Pritchard, B., Prlic, A., Rice, S., Rios, D., Schuster, M., Sealy, I., Slater, G., Smedley, D., Spudich, G., Trevanion, S., Vilella, A.J., Vogel, J., White, S., Wood, M., Birney, E., Cox, T., Curwen, V., Durbin, R., Fernandez-Suarez, X.M., Herrero, J., Hubbard, T.J., Kasprzyk, A., Proctor, G., Smith, J., Ureta-Vidal, A., Searle, S.: Ensembl 2008. Nucleic Acids Res. 36, D707–D714 (2008)
Frishman, D., Mironov, A., Mewes, H.-W., Gelfand, M.: Combining diverse evidence for gene recognition in completely sequenced bacterial genomes. Nucleic Acids Res. 26, 2941–2947 (1998)
Gelfand, M.S.: Computer prediction of the exon-intron structure of mammalian pre-mRNAs. Nucleic Acids Res. 18, 5865–5869 (1990)
Gelfand, M.S., Mironov, A.A., Pevzner, P.A.: Gene recognition via spliced sequence alignment. Proc. Natl. Acad. Sci. USA 93, 9061–9066 (1996)
Gelfand, M.S., Roytberg, M.A.: Prediction of the exon-intron structure by a dynamic programming approach. BioSystems 30, 173–182 (1993)
Gerstein, M.B., Bruce, C., Rozowsky, J.S., Zheng, D., Du, J., Korbel, J.O., Emanuelsson, O., Zhang, Z.D., Wiessman, S., Snyder, M.: What is a gene, post-ENCODE? History and updated definition. Genome Res. 17, 669–681 (2007)
Gish, W., States, D.J.: Identification of protein coding regions by database similarity search. Nat. Genet. 3, 266–272 (1993)
Goffeau, A., Barrell, B.G., Bussey, H., Davis, R.W., Dujon, B., Feldmann, H., Galibert, F., Hoheisel, J.D., Jacq, C., Johnston, M., Louis, E.J., Mewes, H.W., Murakami, Y., Philippsen, P., Tettelin, H., Oliver, S.G.: Life with 6000 genes. Science 274, 563–567 (1996)
Gregory, T.R.: Coincidence, coevolution, or causation? DNA content, cell size, and the C-value enigma. Biol. Rev. 76, 65–101 (2001)
Gregory, T.R.: The C-value enigma in plants and animals: a review of parallels and an appeal for partnership. Ann. Bot. 95, 133–146 (2005)
Gremme, G., Brendel, V., Sparks, M.E., Kurtz, S.: Engineering a software tool for gene structure prediction in higher organisms. Inf. Softw. Tech. 47, 965–978 (2005)
Gross, S.S., Brent, M.R.: Using multiple alignments to improve gene prediction. J. Comput. Biol. 13, 379–393 (2006)
Guigó, R., Knudsen, S., Drake, N., Smith, T.: Prediction of gene structure. J. Mol. Biol. 226, 141–157 (1992)
Guo, F.-B., Ou, H.-Y., Zhang, C.-T.: ZCURVE: a new system for recognizing protein-coding genes in bacterial and archaeal genomes. Nucleic Acids Res. 31, 1780–1789 (2003)
Harrison, P.M., Kumar, A., Lang, N., Snyder, M., Gerstein, M.: A question of size: the eukaryotic proteome and the problems in defining it. Nucleic Acids Res. 30, 1083–1090 (2002)
Henderson, J., Salzberg, S., Fasman, K.H.: Finding genes in DNA with a hidden Markov model. J. Comput. Biol. 4, 127–141 (1997)
Howe, K.L., Chothia, T., Durbin, R.: GAZE: a generic framework for the integration of gene-prediction data by dynamic programming. Genome Res. 12, 1418–1427 (2002)
Hsieh, S.J., Lin, C.Y., Liu, N.H., Chow, W.Y., Tang, C.Y.: GeneAlign: a coding exon prediction tool based on phylogenetical comparisons. Nucleic Acids Res. 34, W280–W284 (2006)
Human genome sequencing consortium: initial sequencing and analysis of the human genome. Nature 409, 745–964 (2002)
Hutchinson, G.B., Hayden, M.R.: The prediction of exons through an analysis of spliceable open reading frames. Nucleic Acids Res. 20, 3453–3462 (1992)
Issac, B., Raghava, G.P.S.: EGPred: prediction of eukaryotic genes uisng ab initio methods after combining with sequence similarity approaches. Genome Res. 14, 1756–1766 (2004)
Kanno, H., Huang, I.-Y., Kan, Y.W., Yoshida, A.: Two structural genes on different chromosomes are required for encoding the major subunit of human red cell glucose-6-phosphate dehydrogenase. Cell 58, 595–606 (1989)
Kellis, M., Patterson, N., Endrizzi, M., Birren, B., Lander, E.S.: Sequencing and comparison of yeast species to identify genes and regulatory elements. Nature 423, 241–254 (2003)
Kim, H., Klein, R., Majewski, J., Ott, J.: Estimating rates of alternative splicing in mammals and invertebrates. Nat. Genet. 36, 915–917 (2004)
Korf, I.: Gene finding in novel genomes. BMC Bioinform. 5, 59 (2004)
Korf, I., Flicek, P., Duan, D., Brent, M.R.: Integrating genomic homology into gene structure prediction. Bioinformatics 17, S140–S148 (2001)
Kowalczuk, M., Mackiewicz, P., Gierlik, A., Dudek, M.R., Cebrat, S.: Total number of coding open reading frames in the yeast genome. Yeast 15, 1031–1034 (1999)
Krogh, A.: Two methods for improving performance of an HMM and their application for gene finding. Proc. Int. Conf. Intell. Syst. Mol. Biol. 5, 179–186 (1997)
Krogh, A.: Using database matches with HMMGene for automated gene detection in Drosophila. Genome Res. 10, 523–528 (2000)
Krogh, A., Brown, M., Mian, I.S., Sjölander, K., Haussler, D.: Hidden Markov models in computational biology: applications to protein modeling. J. Mol. Biol. 235, 1501–1531 (2002)
Krogh, A., Mian, I.S., Haussler, D.: A hidden Markov model that finds genes in E.coli DNA. Nucleic Acids Res. 22, 4768–4778 (1994)
Kulp, D., Haussler, D., Reese, M.G., Eeckman, F.H.: A generalized hidden Markov model for the recognition of human genes in DNA. Proc. Int. Conf. Intell. Syst. Mol. Biol. 4, 134–142 (1996)
Kulp, D., Haussler, D., Reese, M.G., Eeckman, F.H.: Integrating database homology in a probabilistic gene structure model. Pac. Symp. Biocomput. 2, 232–244 (1997)
Kumar, A., Harrison, P.M., Cheung, K.-H., Lan, N., Echols, N., Bertone, P., Miller, P., Gerstein, M.B., Snyder, M.: An integrated approach for finding overlooked genes in yeast. Nat. Biotech. 20, 58–63 (2002)
Larsen, T.S., Krogh, A.: Easy-Gene—a prokaryotic gene finder that ranks ORFs by statistical significance. BMC Bioinform. 4, 21–35 (2003)
Lomsadze, A., Ter-Hovhannisyan, V., Chernoff, Y.O., Borodovsky, M.: Gene identification in novel eukaryotic genomes by self-traning algorithm. Nucleic Acids Res. 33, 6494–6506 (2005)
Mackiewicz, P., Kowalczuk, M., Mackiewicz, D., Nowicka, A., Dudkiewicz, M., Laszkiewicz, A., Dudek, M.R., Cebrat, S.: How many protein-coding genes are there in the Saccharomyces cerevisiae genome? Yeast 19, 619–629 (2002)
Majoros, W.H., Pertea, M., Antonescu, C., Salzberg, S.L.: GlimmerM, Exonomy and Unveil: three ab initio eukaryotic gene finders. Nucleic Acids Res. 31, 3601–3604 (2003)
Majoros, W.H., Pertea, M., Delcher, A.L., Salzberg, S.L.: Efficient decoding algorithms for generalized hidden Markov model gene finders. BMC Bioinform. 6, 16–28 (2005)
Majoros, W.H., Pertea, M., Salzberg, S.L.: TigrScan and GlimmerHMM: two open source ab initio eukaryotic gene finders. Bioinformatics 20, 2878–2879 (2004)
Majoros, W.H., Pertea, M., Salzberg, S.L.: Efficient implementation of a generalized pair hidden Markov model for comparative gene finding. Bioinformatics 21, 1782–1788 (2005)
Mewes, H.W., Heumann, K., Kaps, A., Mayer, K., Pfeiffer, F., Stocker, S., Frishman, D.: MIPS: a database for genomes and protein sequences. Nucleic Acids Res. 27, 44–48 (1999)
Meyer, I.M., Durbin, R.: Comparative ab initio prediction of gene structures using pair HMMs. Bioinformatics 18, 1309–1318 (2002)
Meyer, I.M., Durbin, R.: Gene structure conservation aids similarity based gene prediction. Nucleic Acids Res. 32, 776–783 (2004)
Milanesi, L., D’Angelo, D., Rogozin, I.B.: GeneBuilder: interactive in silico prediction of gene structure. Bioinformatics 15, 612–621 (1999)
Mironov, A.A., Noivchkov, P.S., Gelfand, M.S.: Pro-Frame: similarity-based gene recognition in eukaryotic DNA sequences with errors. Bioinformatics 17, 13–15 (2001)
Mouse Genome Sequencing Consortium: Initial sequencing and comparative analysis of the mouse genome. Nature 420, 520–562 (2002)
Munch, K., Krogh, A.: Automatic generation of gene finders for euakryotic species. BMC Bioinform. 7, 263–274 (2006)
Novichkov, P.S., Gelfand, M.S., Mironov, A.A.: Gene recognition in eukaryotic DNA by comparison of genomic sequences. Bioinformatics 17, 1011–1018 (2001)
Ovcharenko, I., Boffelli, D., Loots, G.G.: eShadow: a tool for comparing closely related sequences. Genome Res. 14, 1191–1198 (2004)
Parra, G., Agarwal, P., Abril, J.F., Wiehe, T., Fickett, J.W., Guigó, R.: Comparative Gene Prediction in Human and Mouse. Genome Res. 13, 108–117 (2003)
Pedersen, J.S., Hein, J.: Gene finding with a hidden Markov model of genome structure and evolution. Bioinformatics 19, 219–227 (2003)
RIKEN genome exploration research group and genome science group (genome network project core group) and the FANTOM consortium. Science 309, 1564–1566 (2005)
Salamov, A.A., Solovyev, V.V.: Ab initio gene finding in Drosophila genomic DNA. Genome Res. 10, 516–522 (2000)
Salzberg, S.L., Delcher, A.L., Fasman, K.H., Henderson, J.: A decision tree system for finding genes in DNA. J. Comput. Biol. 5, 667–680 (1998)
Salzberg, S.L., Delcher, A.L., Kasif, S., White, O.: Microbial gene identification using interpolated Markov models. Nucleic Acids Res. 26, 544–548 (1998)
Schiex, T., Moisan, A., Rouzé, P.: EuGene: an eucaryotic gene finder that combines several sources of evidenc. In: Gascuel, O., Sagot, M.-F. (eds.) Computational Biology, pp. 111–125. Springer, Berlin (2001)
Schweikert, G., Zien, A., Zeller, G., Behr, J., Dieteric, C., Ong, C.S., Philips, P., De Bona, F., Hartmann, L., Bohlen, A., Krüger, N., Sonnenburg, S., Rätsch, G.: mGene: accurate SVM-based gene finding with an application to nematode genomes. Genome Res. June 29 Epub (2009)
Siepel, A., Haussler, D.: Computational identification of evolutionary conserved exons. RECOMB 8, 177–186 (2004)
Smit, A.F.A., Hubley, R., Green, P.: RepeatMasker. http://www.repeatmasker.org
Snyder, E.E., Stormo, G.D.: Identification of coding regions in genomic DNA sequences: an application of dynamic programming and neural networks. Nucleic Acids Res. 21, 607–613 (1993)
Snyder, E.E., Stormo, G.D.: Identification of protein coding regions in genomic DNA. J. Mol. Biol. 248, 1–18 (1995)
Solovyev, V.V., Salamov, A.A., Lawrence, C.B.: Predicting internal exons by oligonucleotide composition and discrimant analysis of spliceable open reading frames. Nucleic Acids Res. 22, 5156–5163 (1994)
Southan, C.: Has the yo-yo stopped? an assessment of human protein-coding gene number. Proteomics 4, 1712–1726 (2004)
Staden, R.: Computer methods to locate signals in nucleic acid sequences. Nucleic Acids Res. 12, 505–519 (1984)
Staden, R., McLachlan, A.D.: Codon preference and its use in identifying protein coding regions in long DNA sequences. Nucleic Acids Res. 10, 141–156 (1982)
Stanke, M., Waack, S.: Gene prediction with a hidden Markov model and a new intron submodel. Bioinformatics 19, ii215–ii225 (2003)
Swift, H.: The constancy of desoxyribose nucleic acid in plant nuclei. Proc. Natl. Acad. Sci. USA 36, 643–654 (1950)
Taher, L., Rinner, O., Garg, S., Sczyrba, A., Brudno, M., Batzoglou, S., Morgenstern, B.: AGenDA: homology-based gene prediction. Bioinformatics 19, 1575–1577 (2003)
Vendrely, R., Vendrely, C.: La teneur du noyau cellulaire en acide désoxyribonucléique à travers les organes, les individus et les espéces animales : Techniques et premiers résultats. Experientia 4, 434–436 (1948)
Wade, N.: Gene sweepstakes end, but winner may well be wrong. New York Times, 3 June 2003
Wain, H.M., Bruford, E.A., Lovering, E.C., Lush, M.J., Wright, M.W., Povey, S.: Guidelines for human gene nomenclature. Genomics 79, 464–470 (2002)
Wiehe, T., Gebauer-Jung, S., Mitchell-Olds, T., Guigó, R.: SGP-1: prediction and validation of homologous genes based on sequence alignments. Genome Res. 11, 1574–1583 (2001)
Wood, V., Rutherford, K.M., Ivens, A., Rajandream, M.-A., Barrell, B.: A re-annotation of the Saccharomyces cerevisiae genome. Comp. Funct. Genomics 2, 143–154 (2001)
Wu, J., Haussler, D.: Coding exon detection using comparative sequences. J. Comput. Biol. 13, 1148–1164 (2006)
Xu, Y., Mural, R.J., Einstein, J.R., Shah, M.B., Uberbacher, E.C.: GRAIL: a multi-agent neural network system for gene identification. Proc. IEEE 84, 1544–1552 (1996)
Xu, Y., Uberbacher, E.C.: In: Salzberg, S.L., Searls, D.B., Kasif, S. (eds.) Computational Methods in Molecular Biology, pp. 109–128. Elsevier Science B.V., Amsterdam (1998)
Yada, T., Takagi, T., Totoki, Y., Sakaki, Y., Takaeda, Y.: DIGIT: a novel gene finding program by combining gene-finders. Pac. Symp. Biocomput. 8, 375–387 (2003)
Zhang, C.-T., Wang, J.: Recognition of protein coding genes in the yeast genome at better than 95 % accuracy based on the Z curve. Nucleic Acids Res. 28, 2804–2814 (2000)
Zhang, M.Q.: Identification of protein coding regions in the human genome by quadratic discriminant analysis. Proc. Natl. Acad. Sci. USA 94, 565–568 (1997)
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2015 Springer-Verlag London
About this chapter
Cite this chapter
Axelson-Fisk, M. (2015). Introduction. In: Comparative Gene Finding. Computational Biology, vol 20. Springer, London. https://doi.org/10.1007/978-1-4471-6693-1_1
Download citation
DOI: https://doi.org/10.1007/978-1-4471-6693-1_1
Published:
Publisher Name: Springer, London
Print ISBN: 978-1-4471-6692-4
Online ISBN: 978-1-4471-6693-1
eBook Packages: Computer ScienceComputer Science (R0)