Limited functional conservation of a global regulator among related bacterial genera: Lrp in Escherichia, Proteus and Vibrio.

Limited functional conservation of a global regulator among related bacterial genera: Lrp in Escherichia, Proteus and Vibrio.
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相关细菌属中全球调节剂的功能保护有限:Escherichia,proteus和Vibrio中的LRP。

DOI:
10.1186/1471-2180-8-60
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发表时间:
2008-04-11
期刊:
影响因子:
4.2
通讯作者:
Blumenthal, Robert M.
Blumenthal, Robert M.
中科院分区:
生物学3区
文献类型:
--
作者:
Lintner, Robert E.;Mishra, Pankaj K.;Srivastava, Poonam;Martinez-Vaz, Betsy M.;Khodursky, Arkady B.;Blumenthal, Robert M.

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细菌基因组序列正在迅速确定,但很少有物种的生理特征。从基因组序列预测调控通常涉及从更好地研究细菌的外推,使用的假设是,保守的调节剂,保守的靶基因,和预测的调节剂结合位点的目标启动子意味着两个物种之间的保守调控。然而,许多被比较的生物在生态和生理上是多样的,外推的限度还没有得到很好的检验。在大肠coliK-12中亮氨酸反应调节蛋白(Lrp)影响约400个基因的表达。奇异变形杆菌和霍乱弧菌具有高度保守的lrp同源基因(与大肠杆菌同源性分别为98%和92%)。coliLRP)。评估了来自这些相关种属的Lrp的功能等效性。异源Lrp在大肠杆菌中调节gltB、livK和lrp的转录融合。大肠杆菌背景以与天然Lrp相同的一般方式,尽管在程度上具有显著差异。这些菌株的微阵列分析表明,异源Lrp蛋白显着影响只有约一半的基因受影响的天然Lrp。在奇异变形杆菌中,异源Lrp恢复了群集,尽管有一些模式差异。奇异变形杆菌比E.大肠杆菌或霍乱弧菌。靶基因直系同源物的Lrp调控在三种天然宿主中不同。引人注目的是,Lrp在E. Lrp在P. mirabilis中表现得更强,但在霍乱弧菌中似乎激活了自己的基因。Lrp直系同源物的调节作用的总体相似性支持将相关菌株之间的外推用于一般目的。然而,该研究还揭示了甚至在具有>90%总体同一性和DNA结合螺旋-转角-螺旋基序的100%同一性的正向异构体调节剂之间的内在差异,以及这些调节剂的量的差异。这些结果表明,预测调控的特定靶基因的基因组序列比较的基础上,单独应该做一个保守的基础上。
Bacterial genome sequences are being determined rapidly, but few species are physiologically well characterized. Predicting regulation from genome sequences usually involves extrapolation from better-studied bacteria, using the hypothesis that a conserved regulator, conserved target gene, and predicted regulator-binding site in the target promoter imply conserved regulation between the two species. However many compared organisms are ecologically and physiologically diverse, and the limits of extrapolation have not been well tested. In E. coli K-12 the leucine-responsive regulatory protein (Lrp) affects expression of ~400 genes. Proteus mirabilis and Vibrio cholerae have highly-conserved lrp orthologs (98% and 92% identity to E. coli lrp). The functional equivalence of Lrp from these related species was assessed. Heterologous Lrp regulated gltB, livK and lrp transcriptional fusions in an E. coli background in the same general way as the native Lrp, though with significant differences in extent. Microarray analysis of these strains revealed that the heterologous Lrp proteins significantly influence only about half of the genes affected by native Lrp. In P. mirabilis, heterologous Lrp restored swarming, though with some pattern differences. P. mirabilis produced substantially more Lrp than E. coli or V. cholerae under some conditions. Lrp regulation of target gene orthologs differed among the three native hosts. Strikingly, while Lrp negatively regulates its own gene in E. coli, and was shown to do so even more strongly in P. mirabilis, Lrp appears to activate its own gene in V. cholerae. The overall similarity of regulatory effects of the Lrp orthologs supports the use of extrapolation between related strains for general purposes. However this study also revealed intrinsic differences even between orthologous regulators sharing >90% overall identity, and 100% identity for the DNA-binding helix-turn-helix motif, as well as differences in the amounts of those regulators. These results suggest that predicting regulation of specific target genes based on genome sequence comparisons alone should be done on a conservative basis.
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