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.
BMC Bioinformatics. 2011 Oct 5;12 Suppl 9(Suppl 9):S19. doi: 10.1186/1471-2105-12-S9-S19.
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.
在原核生物基因组中，转录方向的改变（“CTO”）经常发生。这种变化通常是由于基因组倒位引起的，这可能导致复制和转录方向之间的冲突以及突变率的增加。然而，CTO 并不总是导致复制-转录对抗。此外，CTO 可能导致操纵子结构和/或基因调控的有害破坏。目前存在的 CTO 可能表明选择压力的放松。因此，研究 CTO 是否对受影响基因的进化率有独立影响，以及这些基因在原核生物中是否受到任何类型的选择压力的影响，是很有意义的。
选择三种密切相关的肠杆菌，大肠杆菌、肺炎克雷伯菌和肠炎沙门氏菌 Typhimurium，比较经历转录方向变化（转录方向变化基因，“COGs”）和未经历转录方向变化（转录方向相同基因，“SOGs”）的基因之间的同义（dS）和非同义（dN）替换率。还得出了 dN/dS 比值，以评估分析基因所受到的选择压力。在 COG-SOG 比较中，控制了基因必需性、基因表达水平、复制-转录对抗以及基因末端的 dS 降低等影响进化率估计的混杂因素。
我们证明，在控制了一系列混杂因素后，COGs 的 dN 和 dS 明显高于 SOGs。然而，这两个基因组的 dN/dS 比值相似，这表明 dS 的增加足以解释 COGs 中 dN 的增加。因此，COGs 中进化率的增加可能主要是由突变驱动的。
我们在这里表明，CTO 可以增加受影响基因的进化率。这种影响独立于复制-转录对抗，这被认为是倒位相关进化率增加的主要原因。这种进化率增加的真正原因尚不清楚，但值得进一步探索。
