Soft Shoulders Ahead: Spurious Signatures of Soft and Partial Selective Sweeps Result from Linked Hard Sweeps

Abstract

Characterizing the nature of the adaptive process at the genetic level is a central goal for population genetics. In particular, we know little about the sources of adaptive substitution or about the number of adaptive variants currently segregating in nature. Historically, population geneticists have focused attention on the hard-sweep model of adaptation in which a de novo beneficial mutation arises and rapidly fixes in a population. Recently more attention has been given to soft-sweep models, in which alleles that were previously neutral, or nearly so, drift until such a time as the environment shifts and their selection coefficient changes to become beneficial. It remains an active and difficult problem, however, to tease apart the telltale signatures of hard vs. soft sweeps in genomic polymorphism data. Through extensive simulations of hard-and soft-sweep models, here we show that indeed the two might not be separable through the use of simple summary statistics. In particular, it seems that recombination in regions linked to, but distant from, sites of hard sweeps can create patterns of polymorphism that closely mirror what is expected to be found near soft sweeps. We find that a very similar situation arises when using haplotype-based statistics that are aimed at detecting partial or ongoing selective sweeps, such that it is difficult to distinguish the shoulder of a hard sweep from the center of a partial sweep. While knowing the location of the selected site mitigates this problem slightly, we show that stochasticity in signatures of natural selection will frequently cause the signal to reach its zenith far from this site and that this effect is more severe for soft sweeps; thus inferences of the target as well as the mode of positive selection may be inaccurate. In addition, both the time since a sweep ends and biologically realistic levels of allelic gene conversion lead to errors in the classification and identification of selective sweeps. This general problem of "soft shoulders" underscores the difficulty in differentiating soft and partial sweeps from hard-sweep scenarios in molecular population genomics data. The soft-shoulder effect also implies that the more common hard sweeps have been in recent evolutionary history, the more prevalent spurious signatures of soft or partial sweeps may appear in some genome-wide scans.KEYWORDS natural selection; population genetics; selective sweeps T HERE is a growing body of evidence that positive directional selection has a pervasive impact on genetic variation within and between species (reviewed in Hahn 2008; Sella et al. 2009;Cutter and Payseur 2013). In stark contrast to predictions from Kimura's neutral theory of molecular evolution (Kimura 1968), there is strong evidence that in at least some taxa a large fraction of nucleotide differences between species have been fixed by positive selection (Fay et al. 2001(Fay et al. , 2002Smith and Eyre-Walker 2002;Begun et al. 2007;Boyko et al. 2008;Langley et al. 2012). A great deal of emphasis has there...

Effects of Linked Selective Sweeps on Demographic Inference and Model Selection

“…At increasing distances, both of these statistics recover toward their expectation under neutrality, which they have nearly reached at c/s = 1. At intermediate distances Tajima's D passes through a range where its value is above the expectation of approximately zero, as has been observed previously (Teshima et al 2006;Schrider et al 2015). Under our bottleneck scenario ( Figure 1B Exponential growth is often used to model recent population expansions in lieu of instantaneous population size change, and indeed such growth appears to be a key feature of human population history (Fagundes et al 2007;Gravel et al 2011;Tennessen et al 2012).…”

“…Throughout we have assumed that positive selection occurs only through completed hard selective sweeps. Indeed soft sweeps (Innan and Kim 2004;Hermisson and Pennings 2005;Pennings and Hermisson 2006;Garud et al 2015) and partial sweeps Sabeti et al 2002;Voight et al 2006), may be widespread, and differ in their effects on linked polymorphism (Orr and Betancourt 2001;Meiklejohn et al 2004;Przeworski et al 2005;Teshima et al 2006;Schrider et al 2015;Vy and Kim 2015). Polygenic selection, in which alleles at several different loci underlying a trait under selection will experience a change in frequency, is also thought to be widespread (Pritchard et al 2010;Berg and Coop 2014).…”

Elevated Linkage Disequilibrium and Signatures of Soft Sweeps Are Common in Drosophila melanogaster

“…In the Zambian data, some peaks have a single dominant haplotype, which is consistent with signatures of hard sweeps; while many peaks have multiple frequent haplotypes, consistent with signatures of soft sweeps. This is unlike Raleigh data where multiple high-frequency haplotypes appear at all the top peaks, as we previously observed .In the next section, we will consider several scenarios that can generate the haplotype structure we observe in the data including (i) more complex demographic processes than we have already tested, such as undetected admixture and backflow, (ii) hard sweeps that have decayed early in the sweep trajectory (Messer and Neher 2012;Schrider et al 2015), and (iii) soft sweeps.Could demographic processes generate the bulk of the haplotype structure in Zambian data?We showed earlier in Figure 1 that simple neutral demographic models including bottleneck models, bottlegrowth models, and constant N e models cannot generate the elevated LD and haplotype homozygosity observed in the data. However, it is possible that more complex effects that are not captured by the tested demographic models may be contributing to the elevated H12 values in the data.…”

“…Thus, the soft sweeps we find in the data are likely to be very young. Could the sides of hard sweeps, which have decayed due to recombination events, generate soft-looking sweeps, or soft shoulders (Schrider et al 2015)? In Figure 8 and Figure S8, we measured H12 and H2/H1 values in windows at varying distances away from the center of hard sweeps where the selected site is located.…”

Variation and evolution of the glutamine-rich repeat region of Drosophila Argonaute-2

“…The increase in frequency of the GRR a clade could be due to drift (e.g., during a bottleneck) or selection, such as parasite-mediated selection acting on Ago2 GRR repeat region itself. However, given the known selective history of Ago2 , this distribution of haplotype frequencies could also be explained by incomplete linkage to a nearby hard sweep carrying GRR Hap1 to a high frequency (e.g., Schrider et al 2015).…”