Coding and non-coding DNA thermal stability differences in eukaryotes studied by melting simulation, base shuffling and DNA nearest neighbor frequency analysis

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• 作者：Long ; Dang D. ; Grosse ; Ivo ; Marx ; Kenneth A.
• 关键词：DNA melting simulation ; Exon&ndash ; intron ; Sequence shuffling ; Nearest neighbor frequencies ; Melting temperature
• 刊名：Biophysical Chemistry
• 出版年：2004
• 期刊代码：11_03014622
• 类别：ch
• 出版时间：July 1, 2004
• 卷：110
• 期：1-2
• 页码：25-38
• 文件大小：300 K

摘要

The melting of the coding and non-coding classes of natural DNA sequences was investigated using a program, MELTSIM, which simulates DNA melting based upon an empirically parameterized nearest neighbor thermodynamic model. We calculated T_m results of 8144 natural sequences from 28 eukaryotic organisms of varying F_GC (mole fraction of G and C) and of 3775 coding and 3297 non-coding sequences derived from those natural sequences. These data demonstrated that the T_m vs. F_GC relationships in coding and non-coding DNAs are both linear but have a statistically significant difference (6.6%) in their slopes. These relationships are significantly different from the T_m vs. F_GC relationship embodied in the classical Marmur–Schildkraut–Doty (MSD) equation for the intact long natural sequences. By analyzing the simulation results from various base shufflings of the original DNAs and the average nearest neighbor frequencies of those natural sequences across the F_GC range, we showed that these differences in the T_m vs. F_GC relationships are largely a direct result of systematic F_GC-dependent biases in nearest neighbor frequencies for those two different DNA classes. Those differences in the T_m vs. F_GC relationships and biases in nearest neighbor frequencies also appear between the sequences from multicellular and unicellular organisms in the same coding or non-coding classes, albeit of smaller but significant magnitudes.