Baylor College of Medicine, Houston, Texas, United States of America.
PLoS One. 2011;6(6):e20798. doi: 10.1371/journal.pone.0020798. Epub 2011 Jun 9.
The susceptibility to recombination of a plasmid inserted into a chromosome varies with its genomic position. This recombination position effect is known to correlate with the average G+C content of the flanking sequences. Here we propose that this effect could be mediated by changes in the susceptibility to superhelical duplex destabilization that would occur. We use standard nonparametric statistical tests, regression analysis and principal component analysis to identify statistically significant differences in the destabilization profiles calculated for the plasmid in different contexts, and correlate the results with their measured recombination rates. We show that the flanking sequences significantly affect the free energy of denaturation at specific sites interior to the plasmid. These changes correlate well with experimentally measured variations of the recombination rates within the plasmid. This correlation of recombination rate with superhelical destabilization properties of the inserted plasmid DNA is stronger than that with average G+C content of the flanking sequences. This model suggests a possible mechanism by which flanking sequence base composition, which is not itself a context-dependent attribute, can affect recombination rates at positions within the plasmid.
插入到染色体中的质粒的重组易感性与其基因组位置有关。这种重组位置效应与侧翼序列的平均 G+C 含量相关。在这里,我们提出这种效应可能是由超螺旋双螺旋解链稳定性变化介导的。我们使用标准的非参数统计检验、回归分析和主成分分析,来识别在不同环境下计算出的质粒解链稳定性曲线中的统计学显著差异,并将结果与已测量的重组率进行关联。我们表明,侧翼序列会显著影响质粒内部特定位点的变性自由能。这些变化与实验测量的质粒内部重组率的变化很好地相关。与侧翼序列平均 G+C 含量相比,这种与插入质粒 DNA 的超螺旋解链稳定性特性的重组率相关性更强。该模型提出了一种可能的机制,即侧翼序列碱基组成本身不是依赖于环境的属性,如何影响质粒内位置的重组率。