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Genotype by random environmental interactions gives an advantage to non-favored minor alleles

Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fi...

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Autores principales: Mahdipour-Shirayeh, A., Darooneh, A. H., Long, A. D., Komarova, N. L., Kohandel, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507875/
https://www.ncbi.nlm.nih.gov/pubmed/28701726
http://dx.doi.org/10.1038/s41598-017-05375-0
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author Mahdipour-Shirayeh, A.
Darooneh, A. H.
Long, A. D.
Komarova, N. L.
Kohandel, M.
author_facet Mahdipour-Shirayeh, A.
Darooneh, A. H.
Long, A. D.
Komarova, N. L.
Kohandel, M.
author_sort Mahdipour-Shirayeh, A.
collection PubMed
description Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of fitness varying with respect to both genotype and environment is important in models of cancer initiation and progression, bacterial dynamics, and drug resistance. Under our model spatial heterogeneity redefines the notion of neutrality for a newly arising mutation, as such mutations fix at a higher rate than that predicted under neutrality. The increased fixation probability appears to be due to rare alleles having an advantage. The magnitude of this effect can be large, and is an increasing function of the spatial variance and skew in fitness. The effect is largest when the fitness values of the mutants and wild types are anti-correlated across environments. We discuss results for both a spatial ring geometry of cells (such as that of a colonic crypt), a 2D lattice and a mass-action (complete graph) arrangement.
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spelling pubmed-55078752017-07-14 Genotype by random environmental interactions gives an advantage to non-favored minor alleles Mahdipour-Shirayeh, A. Darooneh, A. H. Long, A. D. Komarova, N. L. Kohandel, M. Sci Rep Article Fixation probability, the probability that the frequency of a newly arising mutation in a population will eventually reach unity, is a fundamental quantity in evolutionary genetics. Here we use a number of models (several versions of the Moran model and the haploid Wright-Fisher model) to examine fixation probabilities for a constant size population where the fitness is a random function of both allelic state and spatial position, despite neither allele being favored on average. The concept of fitness varying with respect to both genotype and environment is important in models of cancer initiation and progression, bacterial dynamics, and drug resistance. Under our model spatial heterogeneity redefines the notion of neutrality for a newly arising mutation, as such mutations fix at a higher rate than that predicted under neutrality. The increased fixation probability appears to be due to rare alleles having an advantage. The magnitude of this effect can be large, and is an increasing function of the spatial variance and skew in fitness. The effect is largest when the fitness values of the mutants and wild types are anti-correlated across environments. We discuss results for both a spatial ring geometry of cells (such as that of a colonic crypt), a 2D lattice and a mass-action (complete graph) arrangement. Nature Publishing Group UK 2017-07-12 /pmc/articles/PMC5507875/ /pubmed/28701726 http://dx.doi.org/10.1038/s41598-017-05375-0 Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Mahdipour-Shirayeh, A.
Darooneh, A. H.
Long, A. D.
Komarova, N. L.
Kohandel, M.
Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title_full Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title_fullStr Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title_full_unstemmed Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title_short Genotype by random environmental interactions gives an advantage to non-favored minor alleles
title_sort genotype by random environmental interactions gives an advantage to non-favored minor alleles
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507875/
https://www.ncbi.nlm.nih.gov/pubmed/28701726
http://dx.doi.org/10.1038/s41598-017-05375-0
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