Effect of genomic distance on coexpression of coregulated genes in E. coli

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Authors

Pannier, Lucia
Merino, Enrique
Marchal, Kathleen
Collado-Vides, Julio

Journal Title

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Publisher

Public Library of Science

Abstract

In prokaryotes, genomic distance is a feature that in addition to coregulation affects coexpression. Several observations, such as genomic clustering of highly coexpressed small regulons, support the idea that coexpression behavior of coregulated genes is affected by the distance between the coregulated genes. However, the specific contribution of distance in addition to coregulation in determining the degree of coexpression has not yet been studied systematically. In this work, we exploit the rich information in RegulonDB to study how the genomic distance between coregulated genes affects their degree of coexpression, measured by pairwise similarity of expression profiles obtained under a large number of conditions. We observed that, in general, coregulated genes display higher degrees of coexpression as they are more closely located on the genome. This contribution of genomic distance in determining the degree of coexpression was relatively small compared to the degree of coexpression that was determined by the tightness of the coregulation (degree of overlap of regulatory programs) but was shown to be evolutionary constrained. In addition, the distance effect was sufficient to guarantee coexpression of coregulated genes that are located at very short distances, irrespective of their tightness of coregulation. This is partly but definitely not always because the close distance is also the cause of the coregulation. In cases where it is not, we hypothesize that the effect of the distance on coexpression could be caused by the fact that coregulated genes closely located to each other are also relatively more equidistantly located from their common TF and therefore subject to more similar levels of TF molecules. The absolute genomic distance of the coregulated genes to their common TF-coding gene tends to be less important in determining the degree of coexpression. Our results pinpoint the importance of taking into account the combined effect of distance and coregulation when studying prokaryotic coexpression and transcriptional regulation.

Description

S1 File. This file contains the following sections: - Selection of a similarity measure to quantify coexpression - Rank-based similarity measures compensate for conditional dependency - The degree of coexpression of genes that are coregulated in E. coli is generally low - Evidence of horizontal gene co-transfer in genes with strong distance conservation (https://doi.org/10.1371/journal.pone.0174887.s001)
S1 Table. List of TFs that control the pairs of coregulated genes used in this study. This table shows all TFs considered in our analysis with at least one pair of coregulated genes (see Materials and methods for the definition of coregulated genes). For each TF we showed the number of pairs of genes coregulated by that TF, the mean distance between every two genes in a pair (in base pairs), and the mean coexpression (as measured by SCR). (https://doi.org/10.1371/journal.pone.0174887.s002)
S2 Table. List of so-called non-coregulated genes that are potentially coregulated as derived from SELEX. This table shows an excerpt of pairs of genes that belong to the negative control of genes not known to be coregulated but highly coexpressed and located nearby and that were predicted to be coregulated according to SELEX. Gene 1 and gene 2 correspond to a pair of genes selected from the set of so-called non-coregulated genes with selection criteria 1) small distance (< 10 kb) 2) high degree of coexpression (SCR<10) and 3) at least one common TF in their respective set of TFs as predicted by SELEX. The coexpression degree between gene 1 and gene 2 is given in SCR. One or more predicted common TF(s) was (were) given. The numbers between brackets refer to the Nth best hit (which means Nth highest % similarity of that TF for that gene) that TF was for respectively gene 1 and gene 2. (https://doi.org/10.1371/journal.pone.0174887.s003)
S3 Table. List of all coregulated genes with their genomic distances and coexpression degrees. This table contains the following fields: TF (coregulating TF), gene 1 (first gene in the pair), gene 2 (second gene in the pair), distance (genomic distance between gene 1 and gene 2), TF-gene1_distance (genomic distance between the TF and the first gene), TF-gene2_distance (genomic distance between the TF and the second gene), role (a = activator, r = repressor, d = dual), SCR (Spearman Correlation Rank as a measure of coexpression degree). (https://doi.org/10.1371/journal.pone.0174887.s004)

Keywords

Genomic clustering, Coexpression, Coregulated genes, TF molecules

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Citation

Pannier L, Merino E, Marchal K, Collado-Vides J (2017) Effect of genomic distance on coexpression of coregulated genes in E. coli. PLoS ONE 12(4): e0174887. https://DOI.org/ 10.1371/journal.pone.0174887.