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The rich phase structure of a mutator model

We propose a modification of the Crow-Kimura and Eigen models of biological molecular evolution to include a mutator gene that causes both an increase in the mutation rate and a change in the fitness landscape. This mutator effect relates to a wide range of biomedical problems. There are three possi...

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Autores principales: Saakian, David B., Yakushkina, Tatiana, Hu, Chin-Kun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056399/
https://www.ncbi.nlm.nih.gov/pubmed/27721395
http://dx.doi.org/10.1038/srep34840
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author Saakian, David B.
Yakushkina, Tatiana
Hu, Chin-Kun
author_facet Saakian, David B.
Yakushkina, Tatiana
Hu, Chin-Kun
author_sort Saakian, David B.
collection PubMed
description We propose a modification of the Crow-Kimura and Eigen models of biological molecular evolution to include a mutator gene that causes both an increase in the mutation rate and a change in the fitness landscape. This mutator effect relates to a wide range of biomedical problems. There are three possible phases: mutator phase, mixed phase and non-selective phase. We calculate the phase structure, the mean fitness and the fraction of the mutator allele in the population, which can be applied to describe cancer development and RNA viruses. We find that depending on the genome length, either the normal or the mutator allele dominates in the mixed phase. We analytically solve the model for a general fitness function. We conclude that the random fitness landscape is an appropriate choice for describing the observed mutator phenomenon in the case of a small fraction of mutators. It is shown that the increase in the mutation rates in the regular and the mutator parts of the genome should be set independently; only some combinations of these increases can push the complex biomedical system to the non-selective phase, potentially related to the eradication of tumors.
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spelling pubmed-50563992016-10-19 The rich phase structure of a mutator model Saakian, David B. Yakushkina, Tatiana Hu, Chin-Kun Sci Rep Article We propose a modification of the Crow-Kimura and Eigen models of biological molecular evolution to include a mutator gene that causes both an increase in the mutation rate and a change in the fitness landscape. This mutator effect relates to a wide range of biomedical problems. There are three possible phases: mutator phase, mixed phase and non-selective phase. We calculate the phase structure, the mean fitness and the fraction of the mutator allele in the population, which can be applied to describe cancer development and RNA viruses. We find that depending on the genome length, either the normal or the mutator allele dominates in the mixed phase. We analytically solve the model for a general fitness function. We conclude that the random fitness landscape is an appropriate choice for describing the observed mutator phenomenon in the case of a small fraction of mutators. It is shown that the increase in the mutation rates in the regular and the mutator parts of the genome should be set independently; only some combinations of these increases can push the complex biomedical system to the non-selective phase, potentially related to the eradication of tumors. Nature Publishing Group 2016-10-10 /pmc/articles/PMC5056399/ /pubmed/27721395 http://dx.doi.org/10.1038/srep34840 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Saakian, David B.
Yakushkina, Tatiana
Hu, Chin-Kun
The rich phase structure of a mutator model
title The rich phase structure of a mutator model
title_full The rich phase structure of a mutator model
title_fullStr The rich phase structure of a mutator model
title_full_unstemmed The rich phase structure of a mutator model
title_short The rich phase structure of a mutator model
title_sort rich phase structure of a mutator model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5056399/
https://www.ncbi.nlm.nih.gov/pubmed/27721395
http://dx.doi.org/10.1038/srep34840
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