Pavlov Sergey, Gursky Vitaly V, Samsonova Maria, Kanapin Alexander, Samsonova Anastasia
Mathematical Biology & Bioinformatics Laboratory, Peter the Great Saint Petersburg Polytechnic University, Saint Petersburg 195251, Russia.
Theoretical Department, Ioffe Institute, Saint Petersburg 194021, Russia.
Life (Basel). 2021 Nov 9;11(11):1209. doi: 10.3390/life11111209.
Transposons are genomic elements that can relocate within a host genome using a 'cut'- or 'copy-and-paste' mechanism. They make up a significant part of many genomes, serve as a driving force for genome evolution, and are linked with Mendelian diseases and cancers. Interactions between two specific retrotransposon types, autonomous (e.g., LINE1/L1) and nonautonomous (e.g., Alu), may lead to fluctuations in the number of these transposons in the genome over multiple cell generations. We developed and examined a simple model of retrotransposon dynamics under conditions where transposon replication machinery competed for cellular resources: namely, free ribosomes and available energy (i.e., ATP molecules). Such competition is likely to occur in stress conditions that a malfunctioning cell may experience as a result of a malignant transformation. The modeling revealed that the number of actively replicating LINE1 and Alu elements in a cell decreases with the increasing competition for resources; however, stochastic effects interfere with this simple trend. We stochastically simulated the transposon dynamics in a cell population and showed that the population splits into pools with drastically different transposon behaviors. The early extinction of active Alu elements resulted in a larger number of LINE1 copies occurring in the first pool, as there was no competition between the two types of transposons in this pool. In the other pool, the competition process remained and the number of L1 copies was kept small. As the level of available resources reached a critical value, both types of dynamics demonstrated an increase in noise levels, and both the period and the amplitude of predator-prey oscillations rose in one of the cell pools. We hypothesized that the presented dynamical effects associated with the impact of the competition for cellular resources inflicted on the dynamics of retrotransposable elements could be used as a characteristic feature to assess a cell state, or to control the transposon activity.
转座子是基因组元件，可利用“切割”或“复制粘贴”机制在宿主基因组内重新定位。它们构成了许多基因组的重要组成部分，是基因组进化的驱动力，并与孟德尔疾病和癌症相关。两种特定类型的逆转录转座子，即自主型（如LINE1/L1）和非自主型（如Alu）之间的相互作用，可能导致这些转座子在多个细胞世代中在基因组中的数量波动。我们开发并检验了一个逆转录转座子动力学的简单模型，该模型处于转座子复制机制竞争细胞资源的条件下：即游离核糖体和可用能量（即ATP分子）。这种竞争很可能发生在功能失调的细胞因恶性转化而可能经历的应激条件下。建模结果显示，随着对资源竞争的增加，细胞中活跃复制的LINE1和Alu元件数量减少；然而，随机效应干扰了这一简单趋势。我们对细胞群体中的转座子动力学进行了随机模拟，结果表明该群体分裂为具有截然不同转座子行为的池。活跃的Alu元件早期灭绝导致第一个池中出现大量LINE1拷贝，因为该池中两种转座子之间没有竞争。在另一个池中，竞争过程持续存在，L1拷贝数量保持较少。随着可用资源水平达到临界值，两种动力学类型均显示噪声水平增加，并且在其中一个细胞池中捕食者 - 猎物振荡的周期和幅度均上升。我们假设，与细胞资源竞争对逆转录转座元件动力学的影响相关的上述动力学效应，可作为评估细胞状态或控制转座子活性的特征。
