Department of Fundamental and Clinical Biochemistry, Kuban State Medical University, Krasnodar 350063, Russia.
Department of Radiophysics and Nanotechnology, Kuban State University, Krasnodar 350040, Russia.
Int J Mol Sci. 2023 Jul 28;24(15):12137. doi: 10.3390/ijms241512137.
The influence of a single H/H replacement on the frequency generation of different-size bubbles in the human interferon alpha-17 gene (IFNA17) under various energies was studied by a developed algorithm and mathematical modeling without simplifications or averaging. This new approach showed the efficacy of researching DNA bubbles and open states both when all hydrogen bonds in nitrogenous base pairs are protium and after an H-substitution. After a single deuterium substitution under specific energies, it was demonstrated that the non-coding region of IFNA17 had a more significant regulatory role in bubble generation in the whole gene than the promoter had. It was revealed that a single deuterium substitution for protium has an influence on the frequency generation of DNA bubbles, which also depends on their size and is always higher for the smaller bubbles under the largest number of the studied energies. Wherein, compared to the natural condition under the same critical value of energy, the bigger raises of the bubble frequency occurrence (maximums) were found for 11-30 base pair (bp) bubbles (higher by 319%), 2-4 bp bubbles (higher by 300%), and 31 bp and over ones (higher by 220%); whereas the most significant reductions of the indicators (minimums) were observed for 11-30 bp bubbles (lower by 43%) and bubbles size over 30 bp (lower by 82%). In this study, we also analyzed the impact of several circumstances on the AT/GC ratio in the formation of DNA bubbles, both under natural conditions and after a single hydrogen isotope exchange. Moreover, based on the obtained data, substantial positive and inverse correlations were revealed between the AT/GC ratio and some factors (energy values, size of DNA bubbles). So, this modeling and variant of the modified algorithm, adapted for researching DNA bubbles, can be useful to study the regulation of replication and transcription in the genes under different isotopic substitutions in the nucleobases.
本文运用一种改进的算法和数学模型，对人类干扰素 alpha-17 基因（IFNA17）在不同能量下不同大小的气泡的频率产生进行了研究，没有进行简化或平均处理。该新方法显示了在氮碱基对中的所有氢键均为氕和 H 取代后，研究 DNA 泡和开放状态的有效性。在特定能量下进行单个氘取代后，结果表明，IFNA17 的非编码区在整个基因的泡生成中比启动子具有更显著的调控作用。结果表明，单个氘取代氕会影响 DNA 泡的频率产生，这也取决于泡的大小，并且在研究的能量数最大的情况下，较小的泡总是更高。其中，与相同能量临界值下的自然条件相比，发现对于 11-30 碱基对（bp）泡（高 319%）、2-4 bp 泡（高 300%）和 31 bp 及以上的泡（高 220%），泡频率发生的最大增加幅度较大；而对于 11-30 bp 泡（低 43%）和超过 30 bp 的泡（低 82%），指标（最小值）的降低幅度最大。在这项研究中，我们还分析了在自然条件下和单个氢同位素交换后，几种情况对 DNA 泡形成中的 AT/GC 比率的影响。此外，根据获得的数据，揭示了 AT/GC 比率与某些因素（能量值、DNA 泡的大小）之间存在实质性的正相关和负相关。因此，这种适用于研究 DNA 泡的建模和修改算法的变体可以用于研究在碱基核苷的不同同位素取代下基因的复制和转录调控。
