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This article is part of the supplement: Proceedings of the Ninth Annual Research in Computational Molecular Biology (RECOMB) Satellite Workshop on Comparative Genomics

Open Access Proceedings

Changes in transcriptional orientation are associated with increases in evolutionary rates of enterobacterial genes

Chieh-Hua Lin12, Chun-Yi Lian1, Chao Agnes Hsiung12* and Feng-Chi Chen1*

Author Affiliations

1 Division of Biostatistics and Bioinformatics, Institute of Population Health Sciences, National Health Research Institutes, 35 Keyen Road, Zhunan Town, Miaoli County, Taiwan, Republic of China

2 Institute of Bioinformatics and Structural Biology, National Tsing Hua University, No. 101, Section 2, Kuang-Fu Road, Hsinchu, Taiwan, Republic of China

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BMC Bioinformatics 2011, 12(Suppl 9):S19  doi:10.1186/1471-2105-12-S9-S19

Published: 5 October 2011



Changes in transcriptional orientation (“CTOs”) occur frequently in prokaryotic genomes. Such changes usually result from genomic inversions, which may cause a conflict between the directions of replication and transcription and an increase in mutation rate. However, CTOs do not always lead to the replication-transcription confrontation. Furthermore, CTOs may cause deleterious disruptions of operon structure and/or gene regulations. The currently existing CTOs may indicate relaxation of selection pressure. Therefore, it is of interest to investigate whether CTOs have an independent effect on the evolutionary rates of the affected genes, and whether these genes are subject to any type of selection pressure in prokaryotes.


Three closely related enterbacteria, Escherichia coli, Klebsiella pneumoniae and Salmonella enterica serovar Typhimurium, were selected for comparisons of synonymous (dS) and nonsynonymous (dN) substitution rate between the genes that have experienced changes in transcriptional orientation (changed-orientation genes, “COGs”) and those that do not (same-orientation genes, “SOGs”). The dN/dS ratio was also derived to evaluate the selection pressure on the analyzed genes. Confounding factors in the estimation of evolutionary rates, such as gene essentiality, gene expression level, replication-transcription confrontation, and decreased dS at gene terminals were controlled in the COG-SOG comparisons.


We demonstrate that COGs have significantly higher dN and dS than SOGs when a series of confounding factors are controlled. However, the dN/dS ratios are similar between the two gene groups, suggesting that the increase in dS can sufficiently explain the increase in dN in COGs. Therefore, the increases in evolutionary rates in COGs may be mainly mutation-driven.


Here we show that CTOs can increase the evolutionary rates of the affected genes. This effect is independent of the replication-transcription confrontation, which is suggested to be the major cause of inversion-associated evolutionary rate increases. The real cause of such evolutionary rate increases remains unclear but is worth further explorations.