The Effect of Strong Purifying Selection on Genetic Diversity
| Autor: | Ivana Cvijovic, Michael M. Desai, Benjamin H. Good |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0106 biological sciences
0301 basic medicine Population Investigations Biology 010603 evolutionary biology 01 natural sciences Coalescent theory Evolution Molecular 03 medical and health sciences Negative selection Gene Frequency Genetics Computer Simulation Selection Genetic Stabilizing selection education education.field_of_study Genetic diversity Models Genetic Computational Biology Genetic Variation Background selection 030104 developmental biology Mutation Genetic Fitness Neutral theory of molecular evolution Neutral mutation |
| Zdroj: | Genetics. 209:1235-1278 |
| ISSN: | 1943-2631 |
| DOI: | 10.1534/genetics.118.301058 |
| Popis: | Negative selection is a ubiquitous evolutionary force, but its effects on diversity in large samples are poorly understood. Cvijović, Good, and Desai obtain simple analytical expressions for the whole population site frequency spectrum.... 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 backward-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. |
| Databáze: | OpenAIRE |
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