Evaluating the ability of the pairwise joint site frequency spectrum to co-estimate selection and demography

Mathew, Lisha; Jensen, Jeffrey D.

doi:10.3389/fgene.2015.00268

“…Positive selection may also affect estimation of multi-population demographic scenarios: though we did not examine this here, Mathew and Jensen recently showed that selective sweeps will impair parameter estimates for a two-population isolation-with-migration model (Mathew and Jensen 2015). Thus our results, combined with those of Mathew and Jenson (2015), Ewing and Jensen (2016), and Messer and Petrov (2013), strongly suggest that the problem of natural selection skewing demographic inference is a general one.…”

Section: Discussionmentioning

confidence: 60%

Effects of linked selective sweeps on demographic inference and model selection

Schrider

¹

,

Shanku

²

,

Kern

³

2016

Preprint

View full text Add to dashboard Cite

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, thereby elucidating population histories. 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 datasets 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. Moreover, we find that selection can lead to incorrect inferences of population size changes when none have occurred. We argue that the amount of recent positive selection required to skew inferences may often be acting in natural populations. These results suggest that demographic studies conducted in many species to date may have exaggerated the extent and frequency of population size changes.3

show abstract

“…As a corollary to this, demographic estimation performed from regions of the genome at differing genetic distances from regions experiencing selection should recover different parameter estimates (Gazave et al 2014). Our results also motivate the challenging task of simultaneous estimation of parameters related to natural selection and demographic history (Eyre-Walker and Keightley 2009; Mathew and Jensen 2015;Sheehan and Song 2016). Until an approach to obtain accurate estimates of demographic parameters in the face of natural selection is devised, population size histories inferred from population genetic data sets from many species may remain substantially biased.…”

Section: Discussionmentioning

confidence: 88%

“…These alternative modes of positive selection could skew demographic inferences in a different manner than what we have observed in this study. Positive selection may also affect estimation of multipopulation demographic scenarios: although we did not examine this here, Mathew and Jensen (2015) recently showed that selective sweeps will impair parameter estimates for a two-population isolationwith-migration model. Thus our results, combined with those of Mathew and Jenson (2015), Ewing and Jensen (2016), and Messer and Petrov (2013), strongly suggest that the problem of natural selection skewing demographic inference is a general one.…”

Section: Discussionmentioning

confidence: 99%

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

Schrider

¹

,

Shanku

²

,

Kern

³

2016

View full text Add to dashboard Cite

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...

show abstract

“…; Excoffier & Foll ; Naduvilezhath et al . ; Mathew & Jensen ) have enabled more accurate inference of demographic history, which can then be used as a null model when scanning for genomic targets of selection. As a result, substantial advances have been made in detecting genes contributing to phenotypic changes in populations that have undergone recent adaptation in the wild such as Drosophila , stickleback, mice and humans (e.g., Reusch et al .…”

Section: Introductionmentioning

confidence: 99%

“…Although disentangling selection and demography remains difficult, the use of population-level, genomescale data from recently diverged natural populations can help to discern the relative impact of these factors. The advent of next-generation sequencing technologies together with new computational and statistical techniques to model demographic histories (Thornton & Andolfatto 2006;Gutenkunst et al 2009;Excoffier & Foll 2011;Naduvilezhath et al 2011;Mathew & Jensen 2015) have enabled more accurate inference of demographic history, which can then be used as a null model when scanning for genomic targets of selection. As a result, substantial advances have been made in detecting genes contributing to phenotypic changes in populations that have undergone recent adaptation in the wild such as Drosophila, stickleback, mice and humans (e.g., Reusch et al 2001;Ihle et al 2006;Domingues et al 2012;Linnen et al 2013) and during domestication (e.g., Doebley 2004;Pollinger et al 2005; reviewed in Stinchcombe & Hoekstra 2008;Ellegren & Sheldon 2008;Mackay et al 2009;Stapley et al 2010).…”

Section: Introductionmentioning

confidence: 99%

The population genomics of rapid adaptation: disentangling signatures of selection and demography in white sands lizards

Laurent

¹

,

Pfeifer

²

,

Settles

³

et al. 2015

Self Cite

View full text Add to dashboard Cite

Understanding the process of adaptation during rapid environmental change remains one of the central focal points of evolutionary biology. The recently formed White Sands system of southern New Mexico offers an outstanding example of rapid adaptation, with a variety of species having rapidly evolved blanched forms on the dunes that contrast with their close relatives in the surrounding dark soil habitat. In this study, we focus on two of the White Sands lizard species, Sceloporus cowlesi and Aspidoscelis inornata, for which previous research has linked mutations in the melanocortin-1 receptor gene (Mc1r) to blanched coloration. We sampled populations both on and off the dunes and used a custom sequence capture assay based on probed fosmid libraries to obtain >50 kb of sequence around Mc1r and hundreds of other random genomic locations. We then used model-based statistical inference methods to describe the demographic and adaptive history characterizing the colonization of White Sands. We identified a number of similarities between the two focal species, including strong evidence of selection in the blanched populations in the Mc1r region. We also found important differences between the species, suggesting different colonization times, different genetic architecture underlying the blanched phenotype and different ages of the beneficial alleles. Finally, the beneficial allele is dominant in S. cowlesi and recessive in A. inornata, allowing for a rare empirical test of theoretically expected patterns of selective sweeps under these differing models.

show abstract

Evaluating the ability of the pairwise joint site frequency spectrum to co-estimate selection and demography

Cited by 14 publications

References 38 publications

Effects of linked selective sweeps on demographic inference and model selection

Effects of linked selective sweeps on demographic inference and model selection

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

The population genomics of rapid adaptation: disentangling signatures of selection and demography in white sands lizards

Contact Info

Product

Resources

About