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PLoS Genet. 2014 Mar 27;10(3):e1004222. doi: 10.1371/journal.pgen.1004222. eCollection 2014 Mar.

Genetic diversity in the interference selection limit.

Author information

1
Departments of Organismic and Evolutionary Biology and of Physics, Harvard University, Cambridge, Massachusetts, United States of America; FAS Center for Systems Biology, Harvard University, Cambridge, Massachusetts, United States of America.
2
CNRS-Laboratoire de Physique Théorique de l'École Normale Supérieure, Paris, France.
3
Max Planck Institute for Developmental Biology, Tübingen, Germany.

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.

PMID:
24675740
PMCID:
PMC3967937
DOI:
10.1371/journal.pgen.1004222
[Indexed for MEDLINE]
Free PMC Article

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