Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources

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...

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Autores principales:	Sergey Pavlov, Vitaly V. Gursky, Maria Samsonova, Alexander Kanapin, Anastasia Samsonova
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	mobile genetic elements retrotransposons cellular resources predator–prey model stochastic dynamics Gillespie algorithm Science Q
Acceso en línea:	https://doaj.org/article/93e4524b0a9e4b9e8986576aaa090dc6
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spelling	oai:doaj.org-article:93e4524b0a9e4b9e8986576aaa090dc62021-11-25T18:11:13ZStochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources10.3390/life111112092075-1729https://doaj.org/article/93e4524b0a9e4b9e8986576aaa090dc62021-11-01T00:00:00Zhttps://www.mdpi.com/2075-1729/11/11/1209https://doaj.org/toc/2075-1729Transposons 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.Sergey PavlovVitaly V. GurskyMaria SamsonovaAlexander KanapinAnastasia SamsonovaMDPI AGarticlemobile genetic elementsretrotransposonscellular resourcespredator–prey modelstochastic dynamicsGillespie algorithmScienceQENLife, Vol 11, Iss 1209, p 1209 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	mobile genetic elements retrotransposons cellular resources predator–prey model stochastic dynamics Gillespie algorithm Science Q
spellingShingle	mobile genetic elements retrotransposons cellular resources predator–prey model stochastic dynamics Gillespie algorithm Science Q Sergey Pavlov Vitaly V. Gursky Maria Samsonova Alexander Kanapin Anastasia Samsonova Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
description	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.
format	article
author	Sergey Pavlov Vitaly V. Gursky Maria Samsonova Alexander Kanapin Anastasia Samsonova
author_facet	Sergey Pavlov Vitaly V. Gursky Maria Samsonova Alexander Kanapin Anastasia Samsonova
author_sort	Sergey Pavlov
title	Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
title_short	Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
title_full	Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
title_fullStr	Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
title_full_unstemmed	Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources
title_sort	stochastic effects in retrotransposon dynamics revealed by modeling under competition for cellular resources
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/93e4524b0a9e4b9e8986576aaa090dc6
work_keys_str_mv	AT sergeypavlov stochasticeffectsinretrotransposondynamicsrevealedbymodelingundercompetitionforcellularresources AT vitalyvgursky stochasticeffectsinretrotransposondynamicsrevealedbymodelingundercompetitionforcellularresources AT mariasamsonova stochasticeffectsinretrotransposondynamicsrevealedbymodelingundercompetitionforcellularresources AT alexanderkanapin stochasticeffectsinretrotransposondynamicsrevealedbymodelingundercompetitionforcellularresources AT anastasiasamsonova stochasticeffectsinretrotransposondynamicsrevealedbymodelingundercompetitionforcellularresources
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Stochastic Effects in Retrotransposon Dynamics Revealed by Modeling under Competition for Cellular Resources

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