Abstract
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.
Highlights
Half of the human genome consists of transposable elements, which were active during different periods of human evolution [4,5]
We considered a mixed model, which combined both types of competition for cellular resources, i.e., ribosomes and energy
The values of the corresponding rate constants orchestrated the transcription and translation processes. Another simplification concerns the fact that the numbers of copies of L1 (L), Alu (S), and the protein coded by L1 (RL ) stochastically evolved within the cellular environment that remained unperturbed
Summary
The type 1 long interspersed element (LINE-1, or L1) provides an excellent example of the autonomous class, accounting for approximately 17% of the human genome [4,11] Another difference between the two types of mobile elements is the way in which transposons utilize cellular molecular machinery for integration into the genome. It may lead to genome size variations induced by the stresses a host cell experiences in disease, which makes it important to study the dynamical equilibrium between the host and the transposons in the context of the bioenergetic balance of a cell [24,25] During their lifecycle, transposable elements may compete for the same pool of resources (energy, etc.) with other essential cellular processes, which makes the cellular environment an important player in the dynamics of retrotransposons. We show which dynamic effects may be expected when the transposons compete for ribosomes and energy
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
