Classic Selective Sweeps Were Rare in Recent Human Evolution

Hernández, Ryan D.; Kelley, Joanna L.; Elyashiv, Eyal; Melton, Samuel; Auton, Adam; McVean, Gilean; Sella, Guy; Przeworski, Molly

doi:10.1126/science.1198878

Cited by 451 publications

(528 citation statements)

References 34 publications

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“…For example, if a human population experienced 1200 recent sweeps fairly evenly spaced across the genome (the equivalent of one recent sweep in 5% of genes), every site in the genome would be within a c/s distance of 0.5 (assuming s = 0.05) from the nearest sweep (i.e., f = 1.0). This is likely an unrealistic scenario in human populations, where positive selection is perhaps less common (Hernandez et al 2011). However, some have argued that selection may be pervasive in the human genome as well (Boyko et al 2008;Enard et al 2014), and certainly humans show many adaptations to local environments (e.g., Li et al 2007;Perry et al 2007;Tishkoff et al 2007;Barreiro et al 2008;Bryk et al 2008).…”

Section: Discussionmentioning

confidence: 99%

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

2016

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The availability of large-scale population genomic sequence data has resulted in an explosion in efforts to infer the demographic histories of natural populations across a broad range of organisms. As demographic events alter coalescent genealogies, they leave detectable signatures in patterns of genetic variation within and between populations. Accordingly, a variety of approaches have been designed to leverage population genetic data to uncover the footprints of demographic change in the genome. The vast majority of these methods make the simplifying assumption that the measures of genetic variation used as their input are unaffected by natural selection. However, natural selection can dramatically skew patterns of variation not only at selected sites, but at linked, neutral loci as well. Here we assess the impact of recent positive selection on demographic inference by characterizing the performance of three popular methods through extensive simulation of data sets with varying numbers of linked selective sweeps. In particular, we examined three different demographic models relevant to a number of species, finding that positive selection can bias parameter estimates of each of these models-often severely. We find that selection can lead to incorrect inferences of population size changes when none have occurred. Moreover, we show that linked selection can lead to incorrect demographic model selection, when multiple demographic scenarios are compared. We argue that natural populations may experience the amount of recent positive selection required to skew inferences. These results suggest that demographic studies conducted in many species to date may have exaggerated the extent and frequency of population size changes.KEYWORDS population genetics; positive selection; demographic inference T HE widespread availability of population genomic data has spurred a new generation of studies aimed at understanding the histories of natural populations from a host of model and nonmodel organisms alike. In particular, genomescale variation data allows for inference of demographic factors such as population size changes, the timing and ordering of population splits, migration rates between populations, and the founding of admixed populations (Pool et al. 2010;Pickrell and Pritchard 2012;Sousa and Hey 2013). Such efforts can refine our picture of demographic events inferred from the archaeological record (e.g., Fagundes et al. 2007;Goebel et al. 2008), or reveal such events in species where no archaeological data are available, and can aid conservation efforts by complementing census data (e.g., Hájková et al. 2007;Garrick et al. 2015).Population genomic data sets are well suited for this task simply because demographic changes leave their mark on patterns of genetic variation. Recent population growth, for example, will result in an excess of rare variation compared to equilibrium expectations (Fu 1997), while population contraction will result in an excess of intermediate frequency alleles (Maruyama and Fuerst 198...

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Section: Discussionmentioning

confidence: 99%

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

2016

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“…Therefore, it is essential to study background selection and understand how its interplay with other evolutionary forces such as demographic changes can shape genomewide patterns of diversity. The importance of this has been highlighted by several recent examinations of DNA sequence polymorphisms in humans (McVicker et al, 2009;Hernandez et al, 2011;Lohmueller et al, 2011), Caenorhabditis (Cutter and Choi, 2010) and rice (Flowers et al, 2012) whereby broad-scale patterns of variability have been found to be compatible with predictions of a background selection model. Furthermore, there is evidence that background selection may explain the observation that the ratio of silent DNA sequence diversity for X-linked loci to that for autosomal loci is approximately one in East African populations of Drosophila melanogaster, instead of the expected value of three quarters (Charlesworth, 2012b).…”

Section: Introductionmentioning

confidence: 91%

A coalescent model of background selection with recombination, demography and variation in selection coefficients

Zeng

2012

Heredity

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There is increasing evidence that background selection, the effects of the elimination of recurring deleterious mutations by natural selection on variability at linked sites, may be a major factor shaping genome-wide patterns of genetic diversity. To accurately quantify the importance of background selection, it is vital to have computationally efficient models that include essential biological features. To this end, a structured coalescent procedure is used to construct a model of background selection that takes into account the effects of recombination, recent changes in population size and variation in selection coefficients against deleterious mutations across sites. Furthermore, this model allows a flexible organization of selected and neutral sites in the region concerned, and has the ability to generate sequence variability at both selected and neutral sites, allowing the correlation between these two types of sites to be studied. The accuracy of the model is verified by checking against the results of forward simulations. These simulations also reveal several patterns of diversity that are in qualitative agreement with observations reported in recent studies of DNA sequence polymorphisms. These results suggest that the model should be useful for data analysis.

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“…A recent analysis of the 1000 Genomes Project data also suggests the plausibility that hard sweeps are rare across humans [51]. Under models of hard sweeps, one expects a reduction in genetic diversity around locations where amino acid substitutions have taken place.…”

Section: Insights From Recent Genomic Studies Of Human Adaptive Evolumentioning

confidence: 99%

“…Under models of hard sweeps, one expects a reduction in genetic diversity around locations where amino acid substitutions have taken place. In the analysis of the 1000 Genomes pilot data, Hernandez et al [51] found the trough in diversity around non-synonymous sites was not lower than that around synonymous substitutions (which serve as a form of internal control for other factors than recent selection affecting diversity). The results suggest that hard sweeps must be uncommon relative to soft sweeps, or if they are common, the selective pressures associated with the hard sweeps must be quite weak.…”

Section: Insights From Recent Genomic Studies Of Human Adaptive Evolumentioning

confidence: 99%

Human population structure and the adaptive response to pathogen-induced selection pressures

Novembre

Han

2012

Phil. Trans. R. Soc. B

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The past few years of research in human evolutionary genetics have provided novel insights and questions regarding how human adaptations to recent selective pressures have taken place. Here, we review the advances most relevant to understanding human evolution in response to pathogen-induced selective pressures. Key insights come from theoretical models of adaptive evolution, particularly those that consider spatially structured populations, and from empirical population genomic studies of adaptive evolution in humans. We also review the CCR5-D32 HIV resistance allele as a case study of pathogen resistance in humans. Taken together, the results make clear that the human response to pathogen-induced selection pressures depends on a complex interplay between the age of the pathogen, the genetic basis of potential resistance phenotypes, and how population structure impacts the adaptive process in humans.

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Classic Selective Sweeps Were Rare in Recent Human Evolution

Cited by 451 publications

References 34 publications

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

A coalescent model of background selection with recombination, demography and variation in selection coefficients

Human population structure and the adaptive response to pathogen-induced selection pressures

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