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, 13 (4), e1002112
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Natural Selection Constrains Neutral Diversity Across a Wide Range of Species

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Natural Selection Constrains Neutral Diversity Across a Wide Range of Species

Russell B Corbett-Detig et al. PLoS Biol.

Abstract

The neutral theory of molecular evolution predicts that the amount of neutral polymorphisms within a species will increase proportionally with the census population size (Nc). However, this prediction has not been borne out in practice: while the range of Nc spans many orders of magnitude, levels of genetic diversity within species fall in a comparatively narrow range. Although theoretical arguments have invoked the increased efficacy of natural selection in larger populations to explain this discrepancy, few direct empirical tests of this hypothesis have been conducted. In this work, we provide a direct test of this hypothesis using population genomic data from a wide range of taxonomically diverse species. To do this, we relied on the fact that the impact of natural selection on linked neutral diversity depends on the local recombinational environment. In regions of relatively low recombination, selected variants affect more neutral sites through linkage, and the resulting correlation between recombination and polymorphism allows a quantitative assessment of the magnitude of the impact of selection on linked neutral diversity. By comparing whole genome polymorphism data and genetic maps using a coalescent modeling framework, we estimate the degree to which natural selection reduces linked neutral diversity for 40 species of obligately sexual eukaryotes. We then show that the magnitude of the impact of natural selection is positively correlated with Nc, based on body size and species range as proxies for census population size. These results demonstrate that natural selection removes more variation at linked neutral sites in species with large Nc than those with small Nc and provides direct empirical evidence that natural selection constrains levels of neutral genetic diversity across many species. This implies that natural selection may provide an explanation for this longstanding paradox of population genetics.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Estimating the impact of selection on linked neutral variation.
To obtain a direct estimate of the amount of linked neutral variation removed by selection, we fit a population genetic model incorporating HH and BGS effects to the estimates of neutral diversity and recombination rate in 500 kb windows across the genome. Model fit (blue), predicted neutral diversity in the absence of selection (red), and observed genetic diversity (dashed) are shown for a species with large population size (Drosophila melanogaster, part A) and small population size (Equus ferus przewalskii, part B). The magnitude of the impact of selection on linked neutral diversity is estimated as 1 – (observed neutral diversity / neutral diversity in the absence of selection). R code to replicate this figure is available at https://github.com/tsackton/linked-selection/blob/master/final_analysis/figure1.R.
Fig 2
Fig 2. The correlation between neutral diversity and recombination rate is stronger in taxonomic classes expected to have larger population sizes.
We computed partial correlations (Kendall's τ) between neutral diversity and recombination rate (estimated in 500 kb windows across the genome), accounting for variation in functional density (measured as proportion of sites in a window that are part of an annotated protein-coding exon). The significance of differences in median τ (red diamonds) between vertebrates and invertebrates, or between woody and herbaceous plants, is based on Wilcoxon Rank Sum Tests. Raw data underlying this figure can be found in S1 Data.
Fig 3
Fig 3. Proxies for census size are correlated with the estimated impact of selection on neutral diversity.
For each species, we obtained estimates of size (in meters) and range (in square kilometers), and used those as predictors in a linear model with a measure of the impact of selection on neutral diversity as the response (see main text and Table 2 for full model information). Both range (part A) and size (part B) are significant predictors of the impact of selection on neutral diversity in the expected directions. Points are colored by kingdom (blue = animals, green = plants), and regression lines estimated independently for plants and animals are shown. Raw data underlying this figure can be found in S2 Data. C) Robustness of our model fit. We tested our main model (see text and Table 2) across a wide range of different analysis options, including different filtering options, different window sizes, and different population genetic parameters. Each point represents the adjusted R2 of the full model for one set of parameter values, colored according to p-value. R code to replicate this analysis is available at: https://github.com/tsackton/linked-selection/blob/master/final_analysis/linear_models.R.
Fig 4
Fig 4. Species with little evidence for selection have smaller census sizes.
For each species, we estimated the relative likelihood of a purely neutral model (no impact of selection on neutral diversity), based on AIC values for neutral and selection models (see methods for details) and categorized species based on support for neutrality (low = relative likelihood < 0.05, medium = relative likelihood ≥ 0.05 but < 0.9, high = relative likelihood ≥ 0.9). Species with more support for neutrality have smaller ranges (part A) and larger body size (part B). p-values for comparisons (indicated by lines at the top of each panel) of low versus high; low versus medium; and low versus medium and high combined are based on Wilcoxon Rank Sum tests (*** p < 0.001, ** p < 0.01, * p < 0.05). Raw data underlying this figure can be found in S2 Data.

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