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The effect of strong purifying selection on genetic diversity

Ivana Cvijović, Benjamin H. Good, Michael M. Desai
doi: https://doi.org/10.1101/211557
Ivana Cvijović
Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138,Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106,
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Benjamin H. Good
Departments of Physics and Bioengineering, University of California, Berkeley CA 94720,Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106,
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Michael M. Desai
Department of Organismic and Evolutionary Biology and FAS Center for Systems Biology, Harvard University, Cambridge, MA 02138,Department of Physics, Harvard University, Cambridge, MA 02138,Kavli Institute for Theoretical Physics, University of California, Santa Barbara, CA 93106,
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Abstract

Purifying selection reduces genetic diversity, both at sites under direct selection and at linked neutral sites. This process, known as background selection, is thought to play an important role in shaping genomic diversity in natural populations. Yet despite its importance, the effects of background selection are not fully understood. Previous theoretical analyses of this process have taken a backwards-time approach based on the structured coalescent. While they provide some insight, these methods are either limited to very small samples or are computationally prohibitive. Here, we present a new forward-time analysis of the trajectories of both neutral and deleterious mutations at a nonrecombining locus. We find that strong purifying selection leads to remarkably rich dynamics: neutral mutations can exhibit sweep-like behavior, and deleterious mutations can reach substantial frequencies even when they are guaranteed to eventually go extinct. Our analysis of these dynamics allows us to calculate analytical expressions for the full site frequency spectrum. We find that whenever background selection is strong enough to lead to a reduction in genetic diversity, it also results in substantial distortions to the site frequency spectrum, which can mimic the effects of population expansions or positive selection. Because these distortions are most pronounced in the low and high frequency ends of the spectrum, they become particularly important in larger samples, but may have small effects in smaller samples. We also apply our forward-time framework to calculate other quantities, such as the ultimate fates of polymorphisms or the fitnesses of their ancestral backgrounds.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 30, 2017.
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The effect of strong purifying selection on genetic diversity
Ivana Cvijović, Benjamin H. Good, Michael M. Desai
bioRxiv 211557; doi: https://doi.org/10.1101/211557
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The effect of strong purifying selection on genetic diversity
Ivana Cvijović, Benjamin H. Good, Michael M. Desai
bioRxiv 211557; doi: https://doi.org/10.1101/211557

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