QST–FST comparisons: evolutionary and ecological insights from genomic heterogeneity

“In contrast to FST, iHS is a within-population measure of recent positive selection that is not affected by the levels of population differentiation (Voight et al., 2006).”

“This strongly suggest that the phenotypic differentiation is driven by selection rather than genetic drift (Leinonen et al., 2013).”

“…STD and AUX covariate models might also be viewed as powerful alternatives to QST–FST comparisons to assess divergence of quantitative traits (see Leinonen et al. 2013, for review) by accurately incorporating genomic information to account for the neutral covariance structure across population…”

“Traditionally, comparisons between divergence of ecologically relevant quantitative traits (QST) and neutral genetic differentiation (FST) have been used to detect selection and local adaptation (McKay & Latta 2002; Leinonen et al. 2013).”

“Further, this marker-specific difference in FST estimates has a major impact on comparative studies of the divergence of quantitative traits, known as QST–FST comparisons, because the inference of the role of natural selection and genetic drift as causes of population genetic differentiation in complex polygenic trait…”

“QST–FST comparisons can make inferences about natural selection on a trait without necessarily having to conduct unwieldy experiments with multiple populations.”

“Furthermore, a recent review found a significant relationship between neutral genetic differentiation and natural selection of phenotypic traits whereby the former is a suitable proxy for estimating complex polygenic traits (Leinonen et al. 2013).”

“…in birds (Ricklefs, Konarzewski & Daan, 1996): estimates of flight metabolism for species with extremely high AR such as performance-gliders like swifts (Lentink & de Kat, 2014) shows that energy expenditure during flight is low compared to species of similar size but smaller AR (Hails, 1979).”

“Field experiments to test the adaptive value of traits in the wild come in a great variety and complexity of forms including QST–FST comparison (Leinonen et al. 2013), reciprocal transplants of hybrid individuals (Lowry et al. 2009), controlled introduction of live organisms to new environments…”

“We performed a comparison of phenotypic and nucleotide levels of divergence to evaluate the putative role of past selective events in shaping the distribution of diversity we report (Leinonen et al., 2013; Whitlock & Guillaume, 2009).”

“A PCA was performed on the traits to consider genetic and/or morphological autocorrelation among traits (Grant & Grant 1995; Kruuk & Garant 2007; Leinonen et al. 2013).”

“…differentiation (FST) and phenotypic differentiation (QST) has been largely used to detect the loci targeted by selection (Le Corre & Kremer, 2012; Leinonen et al., 2013) and several quantitative trait detection methods now include population structure to account for shared neutral trait…”

“To date, most QST-FST comparisons involve studies of non-human adaptation (Leinonen et al 2013).”

“However, genetic divergence in loci influencing variability in adaptive traits is possible even in the absence of differentiation in neutral loci (Le Corre & Kremer 2012; Leinonen et al. 2013).”

“Moreover, it has also been found that physiological divergence may occur in spite of high gene flow (e.g. Leinonen et al., 2013).”

“Instead of using the QST-FST framework (Spitze, 1993; Leinonen et al., 2013), we used a rigorous model-based approach that explicitly incorporates the effects of genetic drift and migration under an island model (Ovaskainen et al., 2011).”

“…of quantitative traits and neutral molecular markers in populations can suggest which evolutionary processes underly population differentiation for multiple quantitative traits: genetic drift, directional selection or uniform selection (McKay and Latta 2002; reviewed in Leinonen et al. 2013).”

“A QST > FST value was regarded as proof of trait divergence outstripping the expectation of a neutral state and thus of a strong directional selection signal (Leinonen et al., 2013).”

“Also, comparative studies of quantitative trait and molecular marker differentiation can be applied to common garden data and used to test whether the observed population divergence exceeds that expected by genetic drift (e.g. Leinonen et al., 2013).”

“Genomics is used to identify genetic variation under natural selection (Mitchell-Olds and Feder, 2003; Leinonen et al., 2013; Grummer et al., 2019) inmodel test organisms, which are accessible to both laboratory and field studies along defined environmental gradients (Spanier et al.”

“S3), which is potentially indicative of 177 polygenic selection acting on the scaling of plant growth (24).”

“…applied to gene expression variation in a few instances 45–49 , accurately estimating the additive genetic basis of gene expression level can be challenging 50 , and there is a tendency for dominance variance to bias Q ST estimates, potentially leading to incorrect inferences of neutrality 44 .”

“To infer whether among-population differences were best explained by neutral or putative selective processes, we contrasted an index of quantitative genetic differentiation (QST) for each probe with that of neutral genetic divergence (Spitze 1993; Leinonen et al. 2013).”

“Finally, comparisons of population differentiation for quantitative traits and genetic markers (FST – QST) may identify signatures of selection (Leinonen et al. 2013).”

“These types of data can be combined for QST −FST (or PST −FST) comparisons to evaluate the contribution of selection v. genetic drift to population differentiation (Holand et al., 2011; Leinonen et al., 2013; Tibblin et al., 2015).”

“, 2005; Bedford and Hartl, 2009) and with a standard QST/FST analysis (Leinonen et al., 2013).”

“Briefly, we aligned the reads for each sample to the D. pseudoobscura reference genome (version 3.04 from FlyBase, ftp://ftp.flybase.net/genomes/Drosophila_pseudoobscura/) using bwa mem version 0.7.17 (Li & Durbin, 2009).”

“If the QST is significantly higher 250 than the neutral FST, it means that the directional selection drives phenotypic divergence and 251 results in ecological adaptation (Miller et al., 2008; Leinonen et al., 2013).”

“The ever-increasing literature comparing differentiation in morphological traits and that at neutral marker loci indicate that phenotypic differentiation is typically greater than neutral genetic differentiation, implying natural selection overcomes ongoing gene flow to maintain morphological differences (Merila & Crn…”

“Q ST (cid:1) F ST comparisons constitute a popular and well-established method for comparing the differentiation in quantitative traits and neutral molecular markers (Meril € a & Crnokrak 2001; McKay & Latta 2002; Leinonen et al. 2008, 2013).”

“We measured epigenetic divergence by computing Pst, the phenotypic differentiation between populations (Pujol et al., 2008; Edelaar et al., 2011; Leinonen et al., 2013), for methylation and expression sites across the genome.”

“In quantitative genetics, divergent trait selection is tested by determining if standardized among- population variance in quantitative traits (‘QST’) exceeds that of neutral loci (‘FST’) (Leinonen et al., 2013).”

“QST is often compared against neutral estimates of population genetic differentiation (FST) from multilocus or genomic data to determine whether phenotypic differences among populations exceed that expected from genetic drift (Meril€a & Crnokrak, 2001; Leinonen et al., 2013).”

“…by directly comparing the allelic variation at QTL in relation to the corresponding trait variation in natural populations (e.g. Peichel et al., 2001; Rogers & Bernatchez, 2005; Hall et al., 2007; Raeymaekers et al., 2007; M€akinen et al., 2008; Kronholm et al., 2012; Liedvogel et al., 2012).”

“Indeed, a value of Qst significantly higher than Fst at neutral loci is generally considered as a signature of diversifying selection on the underlying traits (Leinonen et al. 2013).”

“F ST comparisons; see Whitlock, 2008; Leinonen et al., 2013, for reviews).”

“QST–FST comparisons correct for phylogeographic differentiation and recently have been revised to a multivariate method (Leinonen et al. 2013) that more accurately discriminates neutral from adaptive divergence (Ovaskainen et al.”

“Third, the parameters based on the additive components of variances are a previously published set of parameters that are direct analogs to Wright’s F-statistics (Fst and Fis), a desirable feature that will allow for comparisons between genetic and phenotypic variation [39].”

“Deviations from this expectation can therefore be used to test for the action of natural selection on a quantitative trait (Leinonen et al. 2013; Savolainen et al. 2013).”

“Soon after its introduction the QST–FST comparison has become a routine test for adaptive population divergence (reviewed in Leinonen et al. 2008, 2013; De Kort et al. 2013) despite its recognized methodological limitations (Leinonen et al. 2008; Pujol et al. 2008; Whitlock 2008; Whitlock &…”

“To account for stochastic variation inherent to a neutral model of evolution, we calculated r for a given dental trait or trait combination 1,000 times, each time comparing the DP matrix to different DG matrices arrived at by resampling the microsatellite loci data (23, 62).”

“However, these estimates involve the intra-population variation [57] which can hardly be estimated for lowly sampled populations such as some of ours.”

“…we are able to provide the first formal demonstration of natural selection (but see Shimada et al. 2011) in this extensively studied model system, where earlier studies have provided only indirect indications for adaptive differentiation in a range of quantitative traits (reviewed by Merilä 2013).”

“If the trait evolves neutrally, then QST should be equal to FST (Leinonen et al. 2013).”

“Only a few studies have analysed QST under contrasting growing conditions (or treatments), most of them in animals (Leinonen et al., 2013).”

“…the QST distribution was compared to the extreme tail of the FST distribution: a 95% upper bound was calculated from the mean FST assuming a chisquare distribution with (npopulations – 1) degrees of freedom, that is the Lewontin–Krakauer distribution (Lewontin & Krakauer, 1973; Whitlock, 2008).”

“…[108]; here, suffice to say that F ST , in its sim-plified form, may be expressed as: 2 between þ r 2 within ð 1 Þ where r 2 between is the total genetic variation in a defined locus between populations while r 2 within is the total genetic variation in the same locus within the population [156].”

“QST (Prout & Barker 1993; Spitze 1993) is a commonly used metric of the relative amount of genetic differentiation among populations for quantitative traits (Lynch et al. 1999; Leinonen et al. 2008, 2013; Whitlock 2008).”

“2006), which both may be strong and underlie trait evolution (Leinonen et al. 2013).”

“…in several tree species among-population differentiation at several quantitative (morphological and physiological) traits (mean measured as QST, the among-population differentiation at quantitative, adaptive traits) is higher than GST (Lamy et al. 2012; De Kort et al., 2013; Leinonen et al. 2013).”

“To establish whether differentiation among subpopulations was adaptive, we compared phenotypic differentiation estimated from the common-garden experiment (QST) with the neutral expectation based on microsatellite loci (FST; Leinonen et al. 2013).”

“…the outlier approaches were able to pick up footprints of directional selection; in general, it becomes more difficult to detect signals of adaptive differentiation as the neutral genetic baseline increases (e.g. O’Hara & Meril€a 2005; Leinonen et al. 2008, 2013; Whitlock & Guillaume 2009).”

“Traits exhibiting a significant QST > FST signaled evidence for divergent selection driving among provenance variation [26].”

“Although comparisons of distributions of FST versus PST represent a primary source of evidence for morphological selection (Leinonen et al. 2013), there is little consensus and/ or justification for estimating the necessary confidence intervals.”

“The Q ST of onset of flowering was larger than the F ST in three species ( M. tricuspidata , C. vulgare and L. hispidus ), suggesting directional selection as the most likely responsible evolutionary process (Leinonen et al ., 2013).”

“…between species is an adaptive response to divergent habitats, we performed QST–FST analysis, a method that has been widely used to examine whether natural selection or genetic drift is the main cause of population differentiation in phenotypic traits (McKay and Latta 2002; Leinonen et al. 2013).”

“Thus, the distinction between fitness-related and peripheral (often morphological) traits is not general as the forms of natural selection are different (directional vs. stabilizing) and of different magnitudes (e.g. critically reflected in the QST–FST debate, Leinonen et al., 2013).”

“More data have been published for numerous plant species since this literature review (Lavergne and Molofsky 2007; Leinonen et al. 2013; Wood et al. 2016), making it timely to conduct a new and more precise study.”

“…this heterogeneous differentiation is consistent with the view that has emerged from a totally independent body of work comparing levels of differentiation in neutral marker genes with those in quantitative traits (reviewed in: Meril€a & Crnokrak 2001; Cano et al. 2008; Leinonen et al. 2008, 2013).”