The link between intergenic distances and controls exerted on the transcriptional regulation; an inferential approach

M. Ahmadi; B. Salehi

doi:10.14715/cmb/2017.63.2.3

Issue

Vol. 63 No. 2: Issue 2

Issue Published : March 23, 2017

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The link between intergenic distances and controls exerted on the transcriptional regulation; an inferential approach

https://doi.org/10.14715/cmb/2017.63.2.3

M. Ahmadi

Young Researchers and Elites Club, North Tehran Branch, Islamic Azad University, Tehran, Iran

B. Salehi

Mycobacteriology Research Center, National Research Institute of Tuberculosis and Lung Diseases (NRITLD), Shahid Beheshti University of Medical Sciences, Tehran, Iran

Corresponding Author(s) : B. Salehi

bahar.salehi007@gmail.com

Cellular and Molecular Biology, Vol. 63 No. 2: Issue 2
Article Published : February 28, 2017

Abstract

The position of genes along the genome is an important evolutionary factor for organizing gene regulation. Hence, transcriptional regulatory network have been studied much more extensively from gene distributions rather than other viewpoints. The systematics of intergenic distances, therefore, should be taken into account as an important source of information on the controls exerted on gene expression by various biological mechanisms. Here we study a collection of features including, intergenic and interoperonic distances, distances between isolated genes, distances between regulatory genes and distances between isolated and regulatory genes/operons in order to provide a more informative picture of gene distributions via firstly discovering the statistical model of these features. We find that all these features significantly follow the lognormal distribution. Then we test a few important biological hypotheses particularly in relation to controls exerted in the transcriptional regulatory network in a completely inferential approach using generalized p-value based on the discovered model. We find that mean distances of isolated genes significantly is less than that of regulatory genes. These findings are consistent with the previous evidences that many biological variables, especially in relation to systems biology, follow lognormal distribution. furthermore, our results inferentially support the crucial hypothesis on the two distinct logical types of control, namely digital control (i.e. control mediated by specific transcription factors) and analog control (i.e. control mediated by distribution of supercoiling energy and based on gene neighborhood) previously proposed by studying expression patterns.

Keywords

Lognormal distribution Distances between genes Transcriptional regulatory network Generalized P-value Digital and analog control.

Ahmadi, M., & Salehi, B. (2017). The link between intergenic distances and controls exerted on the transcriptional regulation; an inferential approach. Cellular and Molecular Biology, 63(2), 14–19. https://doi.org/10.14715/cmb/2017.63.2.3

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References

De Martelaere D, Van Gool A. The density distribution of gene loci over the genetic map of Escherichia coli: Its structural, functional and evolutionary implications. Journal of molecular evolution. 1981;17(6):354-60.
Jurka J, Savageau MA. Gene density over the chromosome of Escherichia coli: frequency distribution, spatial clustering, and symmetry. Journal of bacteriology. 1985;163(2):806-11.
Képes F. Periodic transcriptional organization of the E. coli genome. Journal of molecular biology. 2004;340(5):957-64.
Warren P, Ten Wolde P. Statistical analysis of the spatial distribution of operons in the transcriptional regulation network of Escherichia coli. Journal of molecular biology. 2004;342(5):1379-90.
Hermsen R, Ten Wolde PR, Teichmann S. Chance and necessity in chromosomal gene distributions. Trends in Genetics. 2008;24(5):216-9.
Palsson B, Palsson Bí˜. Systems biology: Cambridge university press; 2015.
Gama-Castro S, Jiménez-Jacinto V, Peralta-Gil M, Santos-Zavaleta A, Peñaloza-Spinola MI, Contreras-Moreira B, et al. RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation. Nucleic acids research. 2008;36(suppl 1):D120-D4.
Shen-Orr SS, Milo R, Mangan S, Alon U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature genetics. 2002;31(1):64-8.
Ma H-W, Kumar B, Ditges U, Gunzer F, Buer J, Zeng A-P. An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic acids research. 2004;32(22):6643-9.
Yu H, Gerstein M. Genomic analysis of the hierarchical structure of regulatory networks. Proceedings of the National Academy of Sciences. 2006;103(40):14724-31.
Gutierrez-Rios RM, Rosenblueth DA, Loza JA, Huerta AM, Glasner JD, Blattner FR, et al. Regulatory network of Escherichia coli: consistency between literature knowledge and microarray profiles. Genome research. 2003;13(11):2435-43.
Herrgård MJ, Covert MW. Reconciling gene expression data with known genome-scale regulatory network structures. Genome research. 2003;13(11):2423-34.
Travers A, Muskhelishvili G. DNA supercoiling”a global transcriptional regulator for enterobacterial growth? Nature Reviews Microbiology. 2005;3(2):157-69.
Travers A, Muskhelishvili G. Bacterial chromatin. Current opinion in genetics & development. 2005;15(5):507-14.
Wright MA, Kharchenko P, Church GM, Segrè D. Chromosomal periodicity of evolutionarily conserved gene pairs. Proceedings of the National Academy of Sciences. 2007;104(25):10559-64.
Blot N, Mavathur R, Geertz M, Travers A, Muskhelishvili G. Homeostatic regulation of supercoiling sensitivity coordinates transcription of the bacterial genome. EMBO reports. 2006;7(7):710-5.
Li S, Liberman LM, Mukherjee N, Benfey PN, Ohler U. Integrated detection of natural antisense transcripts using strand-specific RNA sequencing data. Genome research. 2013;23(10):1730-9.
Marr C, Geertz M, Hütt M-T, Muskhelishvili G. Dissecting the logical types of network control in gene expression profiles. BMC systems biology. 2008;2(1):18.
Sonnenschein N, Hütt M-T, Stoyan H, Stoyan D. Ranges of control in the transcriptional regulation of Escherichia coli. BMC systems biology. 2009;3(1):1.
Krishnamoorthy K, Mathew T. Inferences on the means of lognormal distributions using generalized p-values and generalized confidence intervals. Journal of statistical planning and inference. 2003;115(1):103-21.

References

De Martelaere D, Van Gool A. The density distribution of gene loci over the genetic map of Escherichia coli: Its structural, functional and evolutionary implications. Journal of molecular evolution. 1981;17(6):354-60.

Jurka J, Savageau MA. Gene density over the chromosome of Escherichia coli: frequency distribution, spatial clustering, and symmetry. Journal of bacteriology. 1985;163(2):806-11.

Képes F. Periodic transcriptional organization of the E. coli genome. Journal of molecular biology. 2004;340(5):957-64.

Warren P, Ten Wolde P. Statistical analysis of the spatial distribution of operons in the transcriptional regulation network of Escherichia coli. Journal of molecular biology. 2004;342(5):1379-90.

Hermsen R, Ten Wolde PR, Teichmann S. Chance and necessity in chromosomal gene distributions. Trends in Genetics. 2008;24(5):216-9.

Palsson B, Palsson Bí˜. Systems biology: Cambridge university press; 2015.

Gama-Castro S, Jiménez-Jacinto V, Peralta-Gil M, Santos-Zavaleta A, Peñaloza-Spinola MI, Contreras-Moreira B, et al. RegulonDB (version 6.0): gene regulation model of Escherichia coli K-12 beyond transcription, active (experimental) annotated promoters and Textpresso navigation. Nucleic acids research. 2008;36(suppl 1):D120-D4.

Shen-Orr SS, Milo R, Mangan S, Alon U. Network motifs in the transcriptional regulation network of Escherichia coli. Nature genetics. 2002;31(1):64-8.

Ma H-W, Kumar B, Ditges U, Gunzer F, Buer J, Zeng A-P. An extended transcriptional regulatory network of Escherichia coli and analysis of its hierarchical structure and network motifs. Nucleic acids research. 2004;32(22):6643-9.

Yu H, Gerstein M. Genomic analysis of the hierarchical structure of regulatory networks. Proceedings of the National Academy of Sciences. 2006;103(40):14724-31.

Gutierrez-Rios RM, Rosenblueth DA, Loza JA, Huerta AM, Glasner JD, Blattner FR, et al. Regulatory network of Escherichia coli: consistency between literature knowledge and microarray profiles. Genome research. 2003;13(11):2435-43.

Herrgård MJ, Covert MW. Reconciling gene expression data with known genome-scale regulatory network structures. Genome research. 2003;13(11):2423-34.

Travers A, Muskhelishvili G. DNA supercoiling”a global transcriptional regulator for enterobacterial growth? Nature Reviews Microbiology. 2005;3(2):157-69.

Travers A, Muskhelishvili G. Bacterial chromatin. Current opinion in genetics & development. 2005;15(5):507-14.

Wright MA, Kharchenko P, Church GM, Segrè D. Chromosomal periodicity of evolutionarily conserved gene pairs. Proceedings of the National Academy of Sciences. 2007;104(25):10559-64.

Blot N, Mavathur R, Geertz M, Travers A, Muskhelishvili G. Homeostatic regulation of supercoiling sensitivity coordinates transcription of the bacterial genome. EMBO reports. 2006;7(7):710-5.

Li S, Liberman LM, Mukherjee N, Benfey PN, Ohler U. Integrated detection of natural antisense transcripts using strand-specific RNA sequencing data. Genome research. 2013;23(10):1730-9.

Marr C, Geertz M, Hütt M-T, Muskhelishvili G. Dissecting the logical types of network control in gene expression profiles. BMC systems biology. 2008;2(1):18.

Sonnenschein N, Hütt M-T, Stoyan H, Stoyan D. Ranges of control in the transcriptional regulation of Escherichia coli. BMC systems biology. 2009;3(1):1.

Krishnamoorthy K, Mathew T. Inferences on the means of lognormal distributions using generalized p-values and generalized confidence intervals. Journal of statistical planning and inference. 2003;115(1):103-21.

Author biographies is not available.