Abstract
Genomic clustering of functionally interrelated genes is not unusual in eukaryotes. In such clusters, co-localized genes are co-regulated and often belong to the same pathway. However, biochemical details are still unknown in many cases, hence computational prediction of clusters’ structures is beneficial for understanding their functions. Yet, in silico detection of eukaryotic gene clusters (eGCs) remains a challenging task. We suggest a novel method for eGC detection based on consideration of cluster-specific regulatory patterns. The basic idea is to differentiate cluster from non-cluster genes by regulatory elements within their promoter sequences using the density of cluster-specific motifs’ occurrences (which is higher within the cluster region) as an additional distinguishing feature. The effectiveness of the method was demonstrated by successful re-identification of functionally characterized clusters. It is also applicable to the detection of yet unknown eGCs. Additionally, the method provides valuable information about the binding sites for cluster-specific regulators.
Chapter PDF
Similar content being viewed by others
Keywords
References
Blumenthal, T.: Gene clusters and polycistronic transcription in eukaryotes. Bioessays 20, 480–487 (1998)
Lee, J.M., Sonnhammer, E.L.: Genomic gene clustering analysis of pathways in eukaryotes. Genome Res. 13, 875–882 (2003)
Caron, H., van Schaik, B., van der Mee, M., Baas, F., Riggins, G., van Sluis, P., Hermus, M.C., van Asperen, R., Boon, K., Voute, P.A., Heiqsterkamp, S., van Kampen, A., Versteeg, R.: The human transcriptome map: Clustering of highly expressed genes in chromosomal domains. Science 291, 1289–1292 (2001)
Spellman, P.T., Rubin, G.M.: Evidence for large domains of similarly expressed genes in the Drosophila genome. J. Biol. 1, 5 (2002)
Sasso, S., Pohnert, G., Lohr, M., Mittag, M., Hertweck, C.: Microalgae in the postgenomic era: a blooming reservoir for new natural products. FEMS Microbiol. Rev. 36, 761–785 (2012)
Brakhage, A.A., Schroeckh, V.: Fungal secondary metabolites - strategies to activate silent gene clusters. Fungal Genet. Biol. 48, 15–22 (2011)
Keller, N.P., Hohn, T.M.: Metabolic Pathway Gene Clusters in Filamentous Fungi. Fungal Genet. Biol. 21, 17–29 (1997)
Brakhage, A.A.: Regulation of fungal secondary metabolism. Nat. Rev. Microbiol. 11, 21–32 (2013)
Hoffmeister, D., Keller, N.P.: Natural products of filamentous fungi: enzymes, genes, and their regulation. Nat. Prod. Rep. 24, 393–416 (2007)
Yi, G., Sze, S.H., Thon, M.R.: Identifying clusters of functionally related genes in genomes. Bioinformatics 23, 1053–1060 (2007)
Schroeckh, V., Scherlach, K., Nützmann, H.W., Shelest, E., Schmidt-Heck, W., Schuemann, J., Martin, K., Hertweck, C., Brakhage, A.A.: Intimate bacterial-fungal interaction triggers biosynthesis of archetypal polyketides in Aspergillus nidulans. Proc. Natl. Acad. Sci. USA 106, 14558–14563 (2009)
Khaldi, N., Seifuddin, F.T., Turner, G., Haft, D., Nierman, W.C., Wolfe, K.H., Fedorova, N.D.: SMURF: Genomic mapping of fungal secondary metabolite clusters. Fungal Genet. Biol. 47, 736–741 (2010)
Medema, M.H., Blin, K., Cimermancic, P., de Jager, V., Zakrzewski, P., Fischbach, M.A., Weber, T., Takano, E., Breitling, R.: antiSMASH: rapid identification, annotation and analysis of secondary metabolite biosynthesis gene clusters in bacterial and fungal genome sequences. Nucleic Acids Res 39, W339–W346 (2011)
Fedorova, N.D., Moktali, V., Medema, M.H.: Bioinformatics approaches and software for detection of secondary metabolic gene clusters. Methods Mol. Biol. 944, 23–45 (2012)
Do, J.H., Miyano, S., The, G.C.: window-averaged DNA curvature profile of secondary metabolite gene cluster in Aspergillus fumigatus genome. Appl. Microbiol. Biotechnol. 80, 841–847 (2008)
Bailey, T.L., Boden, M., Buske, F.A., Frith, M., Grant, C.E., Clementi, L., Ren, J., Li, W.W., Noble, W.S.: MEME SUITE: tools for motif discovery and searching. Nucleic Acids Res. 37, W202–W208 (2009)
Amaike, S., Keller, N.P.: Aspergillus flavus. Annu. Rev. Phytopathol. 49, 107–133 (2011)
Aspergillus Comparative Sequencing Project, Broad Institute of Harvard and MIT, http://www.broadinstitute.org/
Gerke, J., Bayram, O., Feussner, K., Landesfeind, M., Shelest, E., Feussner, I., Braus, G.H.: Breaking the silence: protein stabilization uncovers silenced biosynthetic gene clusters in the fungus Aspergillus nidulans. Appl. Environ. Microbiol. 78, 8234–8244 (2012)
Arnaud, M.B., Chibucos, M.C., Costanzo, M.C., Crabtree, J., Inglis, D.O., Lotia, A., Orvis, J., Shah, P., Skrzypek, M.S., Binkley, G., Miyasato, S.R., Wortman, J.R., Sherlock, G.: The Aspergillus Genome Database, a curated comparative genomics resource for gene, protein and sequence information for the Aspergillus research community. Nucleic Acids Res. 38, D420–D427 (2010)
Bergmann, S., Funk, A.N., Scherlach, K., Schroeckh, V., Shelest, E., Horn, U., Hertweck, C., Brakhage, A.A.: Activation of a silent fungal polyketide biosynthesis pathway through regulatory cross talk with a cryptic nonribosomal peptide synthetase gene cluster. Appl. Environ. Microbiol. 76, 8143–8149 (2010)
Bergmann, S., Schümann, J., Scherlach, K., Lange, C., Brakhage, A., Hertweck, C.: Genomics driven discovery of PKS-NRPS hybrid metabolites from Aspergillus nidulans. Nat. Chem. Biol. 3, 213–217 (2007)
Gardiner, D.M., Howlett, B.: Bioinformatic and expression analysis of the putative gliotoxin biosynthetic gene cluster of Aspergillus fumigatus. FEMS Microbiol. Lett. 248, 241–248 (2005)
Imamura, K., Tsuyama, Y., Hirata, T., Shiraishi, S., Sakamoto, K., Yamada, O., Akita, O., Shimoi, H.: Identification of a Gene Involved in the Synthesis of a Dipeptidyl Peptidase IV Inhibitor in Aspergillus oryzae. Appl. Environ. Microbiol. 78, 6996–7002 (2012)
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Wolf, T., Shelest, V., Shelest, E. (2013). Motif-Based Method for the Genome-Wide Prediction of Eukaryotic Gene Clusters. In: Petrosino, A., Maddalena, L., Pala, P. (eds) New Trends in Image Analysis and Processing – ICIAP 2013. ICIAP 2013. Lecture Notes in Computer Science, vol 8158. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-41190-8_42
Download citation
DOI: https://doi.org/10.1007/978-3-642-41190-8_42
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-41189-2
Online ISBN: 978-3-642-41190-8
eBook Packages: Computer ScienceComputer Science (R0)