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Genetic diversity in the interference selection limit

Good, Benjamin H. and Walczak, Aleksandra M. and Neher, Richard A. and Desai, Michael M.. (2014) Genetic diversity in the interference selection limit. PLoS Genetics, 10 (3). e1004222.

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Abstract

Pervasive natural selection can strongly influence observed patterns of genetic variation, but these effects remain poorly understood when multiple selected variants segregate in nearby regions of the genome. Classical population genetics fails to account for interference between linked mutations, which grows increasingly severe as the density of selected polymorphisms increases. Here, we describe a simple limit that emerges when interference is common, in which the fitness effects of individual mutations play a relatively minor role. Instead, similar to models of quantitative genetics, molecular evolution is determined by the variance in fitness within the population, defined over an effectively asexual segment of the genome (a "linkage block"). We exploit this insensitivity in a new "coarse-grained" coalescent framework, which approximates the effects of many weakly selected mutations with a smaller number of strongly selected mutations that create the same variance in fitness. This approximation generates accurate and efficient predictions for silent site variability when interference is common. However, these results suggest that there is reduced power to resolve individual selection pressures when interference is sufficiently widespread, since a broad range of parameters possess nearly identical patterns of silent site variability.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Computational Modeling of Biological Processes (Neher)
UniBasel Contributors:Neher, Richard
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
ISSN:1553-7390
e-ISSN:1553-7404
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:17 Sep 2019 06:26
Deposited On:04 Dec 2017 08:15

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