Natural Selection Constrains Neutral Diversity across A Wide Range of Species
Russell B. Corbett-Detig, Daniel L. Hartl, Timothy B. Sackton
Published: April 10, 2015DOI: 10.1371/journal.pbio.1002112
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.
A fundamental goal of population genetics is to understand why levels of genetic diversity vary among species and populations. Under the assumptions of the neutral model of molecular evolution, the amount of variation present in a population should be directly proportional to the size of the population. However, this prediction does not tally with real-life observations: levels of genetic diversity are found to be substantially more uniform, even among species with widely differing population sizes, than expected. Because natural selection—which removes genetically linked neutral variation—is more efficient in larger populations, selection on novel mutations offers a potential reconciliation of this paradox. In this work, we align and jointly analyze whole genome genetic variation data from a wide variety of species. Using this dataset and population genetic models of the impact of selection on neutral variation, we test the prediction that selection will disproportionally remove neutral variation in species with large population sizes. We show that genomic signature of natural selection is pervasive across most species, and that the amount of linked neutral variation removed by selection correlates with proxies for population size. We propose that pervasive natural selection constrains neutral diversity and provides an explanation for why neutral diversity does not scale as expected with population size.
Citation: Corbett-Detig RB, Hartl DL, Sackton TB (2015) Natural Selection Constrains Neutral Diversity across A Wide Range of Species. PLoS Biol 13(4): e1002112. doi:10.1371/journal.pbio.1002112
Academic Editor: Nick H. Barton, Institute of Science and Technology Austria (IST Austria), AUSTRIA
Received: December 17, 2014; Accepted: February 20, 2015; Published: April 10, 2015
Copyright: © 2015 Corbett-Detig et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: Data and code associated with this manuscript are available from Github at https://github.com/tsackton/linked-selection.
Funding: This work was supported in part by National Institute of Health grants R01GM084236, AI099105 and AI106734 to DLH. During this work, RBCD was supported by Harvard Prize Graduate Fellowship and a UCB Chancellor’s Postdoctoral Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AIC, Akaike Information Criteria; BGS, background selection; BLAST, Basic Local Alignment Search Tool; Nc, census population size; GFF, general feature format; GOLD, Genomes OnLine Database; HH, hitchhiking; NCBI, National Center for Biotechnology Information; PCR, polymerase chain reaction
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