title: Alternative splicing can lead to chaos.
abstract: Alternative splicing is a widespread phenomenon in higher eukaryotes, where it serves as a mechanism to increase the functional diversity of proteins. This phenomenon has been described for different classes of proteins, including transcription regulatory proteins. We demonstrated that in the simplest genetic system model the formation of the alternatively spliced isoforms with opposite functions (activators and repressors) could be a cause of transition to chaotic dynamics. Under the simplest genetic system we understand a system consisting of a single gene encoding the structure of a transcription regulatory protein whose expression is regulated by a feedback mechanism. As demonstrated by numerical analysis of the models, if the synthesized isoforms regulate the expression of their own gene acting through different sites and independently of each other, for the generation of chaotic dynamics it is sufficient that the regulatory proteins have a dimeric structure. If regulatory proteins act through one site, the chaotic dynamics is generated in the system only when the repressor protein is either a tetrameric or a higher-dimensional multimer. In this case the activator can be a dimer. It was also demonstrated that if the transcription factor isoforms exhibit either activating or inhibiting activity and are lower-dimensional multimers (< 4), independently of the regulation type the model demonstrates either cyclic or stationary trajectories.
authors.affiliation: Institute of Cytology and Genetics, Siberian Branch, Russian Academy of Sciences, pr. Lavrentieva 10, Novosibirsk 630090, Russia , Novosibirsk State University, av. Pirogova 2, Novosibirsk 630090, Russia.
authors.forename: Vitaly A
authors.initials: VA
authors.lastname: Likhoshvai
authors.forename: Vladislav V
authors.initials: VV
authors.lastname: Kogai
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Fadeev
authors.forename: Tamara M
authors.initials: TM
authors.lastname: Khlebodarova
mesh_terms: D017398:Alternative Splicing; D005246:Feedback; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D008957:Models, Genetic; D020033:Protein Isoforms / Q000235:genetics; D011506:Proteins / Q000235:genetics; D026362:Serum Response Factor / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D011506:Proteins; D026362:Serum Response Factor
keywords: Modeling; alternative splicing; deterministic chaos; gene networks