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Estimating the Genome-Wide Contribution of Selection to Temporal Allele Frequency Change

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Estimating the Genome-Wide Contribution of Selection to Temporal Allele Frequency Change Estimating the genome-wide contribution of selection to temporal allele frequency change Vince Buffaloa,b,1 and Graham Coopb aPopulation Biology Graduate Group, University of California, Davis, CA 95616; and bCenter for Population Biology, Department of Evolution and Ecology, University of California, Davis, CA 95616 Edited by Montgomery Slatkin, University of California, Berkeley, CA, and approved July 13, 2020 (received for review October 31, 2019) Rapid phenotypic adaptation is often observed in natural popula- a polygenic trait (such as fitness) is distributed across numerous tions and selection experiments. However, detecting the genome- loci. This can lead to subtle allele frequency shifts on standing wide impact of this selection is difficult since adaptation often variation that are difficult to distinguish from background lev- proceeds from standing variation and selection on polygenic els of genetic drift and sampling variance. Increasingly, genomic traits, both of which may leave faint genomic signals indistin- experimental evolution studies with multiple time points, and guishable from a noisy background of genetic drift. One promis- in some cases multiple replicate populations, are being used ing signal comes from the genome-wide covariance between to detect large-effect selected loci (30, 31) and differentiate allele frequency changes observable from temporal genomic data modes of selection (32–34). In addition, these temporal–genomic (e.g., evolve-and-resequence studies). These temporal covariances studies have begun in wild populations, some with the goal of reflect how heritable fitness variation in the population leads finding variants that exhibit frequency changes consistent with changes in allele frequencies at one time point to be predic- fluctuating selection (35, 36). In a previous paper, we pro- tive of the changes at later time points, as alleles are indirectly posed that one useful signal for understanding the genome-wide selected due to remaining associations with selected alleles. Since impact of polygenic linked selection detectable from temporal genetic drift does not lead to temporal covariance, we can use genomic data is the temporal autocovariance (i.e., covariance these covariances to estimate what fraction of the variation in between two time points) of allele frequency changes (37). These allele frequency change through time is driven by linked selec- covariances are created when the loci that underly heritable tion. Here, we reanalyze three selection experiments to quantify fitness variation perturb the frequencies of linked alleles; in the effects of linked selection over short timescales using covari- contrast, when genetic drift acts alone in a closed population, ance among time points and across replicates. We estimate that these covariances are expected to be zero for neutral alleles. at least 17 to 37% of allele frequency change is driven by selec- Mathematically, temporal covariances are useful because it is tion in these experiments. Against this background of positive natural to decompose the total variance in allele frequency genome-wide temporal covariances, we also identify signals of change across a time interval into the variances and covari- negative temporal covariance corresponding to reversals in the ances in allele frequency change between generations. Further- direction of selection for a reasonable proportion of loci over more, biologically, these covariances reflect the extent to which the time course of a selection experiment. Overall, we find that allele frequency changes in one generation predict changes in in the three studies we analyzed, linked selection has a large another due to shared selection pressures and associations with impact on short-term allele frequency dynamics that is readily selected loci. distinguishable from genetic drift. Significance linked selection j experimental evolution j adaptation A long-standing problem in evolutionary biology is to under- long-standing problem in evolutionary genetics is quan- stand the processes that shape the genetic composition of Atifying the roles of genetic drift and selection in shaping populations. In a population without migration, two pro- genome-wide allele frequency changes. Selection can affect allele cesses that change allele frequencies are selection, which frequencies, both directly and indirectly, with the indirect effect increases beneficial alleles and removes deleterious ones, and coming from the action of selection on correlated loci elsewhere genetic drift, which randomly changes frequencies as some in genome [e.g., linked selection (1–4); ref. 5 has a review]. Previ- parents contribute more or fewer alleles to the next gener- ous work has mostly focused on teasing apart the impacts of drift ation. Previous efforts to disentangle these processes have and selection on genome-wide diversity using population sam- used genomic samples from a single time point and models ples from a single contemporary time point, often by modeling of how selection affects neighboring sites (linked selection). the correlation between regional recombination rate, gene den- Here, we use genomic data taken through time to quantify sity, and diversity created in the presence of linked selection (6, contributions of selection and drift to genome-wide frequency 7). This approach has shown that linked selection has a major changes. We show that selection acts over short timescales role in shaping patterns of genome-wide diversity across the in three evolve-and-resequence studies and has a sizable genomes of a range of sexual species (8–16) and has allowed us genome-wide impact. to quantify the relative influence of positive selection (hitchhik- ing) and negative selection (background selection) (8, 9, 16–19). Author contributions: V.B. and G.C. designed research; V.B. performed research; V.B. con- However, we lack an understanding of both how linked selection tributed new reagents/analytic tools; V.B. analyzed data; and V.B. and G.C. wrote the acts over short time intervals and its full impact on genome-wide paper.y allele frequency changes. The authors declare no competing interest.y There are numerous examples of rapid phenotypic adapta- This article is a PNAS Direct Submission.y tion (20–23) and rapid, selection-driven genomic evolution in Published under the PNAS license.y asexual populations (24–26). Yet, the polygenic nature of fit- 1 To whom correspondence may be addressed. Email: [email protected] ness makes detecting the impact of selection on genome-wide This article contains supporting information online at https://www.pnas.org/lookup/suppl/ variation over short timescales in sexual populations remark- doi:10.1073/pnas.1919039117/-/DCSupplemental.y ably difficult (27–29). This is because the effect of selection on First published August 12, 2020. 20672–20680 j PNAS j August 25, 2020 j vol. 117 j no. 34 www.pnas.org/cgi/doi/10.1073/pnas.1919039117 Downloaded by guest on September 27, 2021 Here, we provide empirical analyses to quantify the impact replicates. Each row of these matrices represents the tempo- of linked selection acting over short timescales (tens of gener- ral covariance Cov(∆10 ps , ∆10 pt ) between the allele frequency ations) across two evolve-and-resequence studies (33, 38) and an change (in 10-generation intervals, denoted ∆10 pt ) of some ini- artificial selection experiment (39). These sequencing selection tial reference generation s (the row of the matrix) and some experiments have started to uncover selected loci contribut- later time point t (the column of the matrix). We corrected ing to the adaptive response; however, it is as yet far from these matrices for biases created due to sampling noise and clear how much of genome-wide allele frequency changes are normalized the entries for heterozygosity (SI Appendix, sections driven by selection or genetic drift. We repeatedly find a signal S1.2 and S1.4). These covariances are expected to be zero when of temporal covariance, consistent with linked selection acting only drift is acting, as only heritable variation for fitness can to significantly perturb genome-wide allele frequency changes create covariance between allele frequency changes in a closed across the genome in a manner that other approaches would population (37). Averaging across the 10 replicate temporal not be able differentiate from genetic drift. We estimate a lower covariances matrices, we find temporal covariances that are sta- bound of the fraction of variance in allele frequency change tistically significant (95% block bootstraps CIs do not contain caused by selection, as well as the correlation between allele zero), consistent with linked selection perturbing genome-wide frequency changes between replicate populations caused by con- allele frequency changes over very short time periods. The vergent selection pressures. Overall, we demonstrate that linked covariances between all adjacent time intervals are positive and selection has a powerful role in shaping genome-wide allele then decay toward zero as we look at more distant time intervals frequency changes over very short timescales in experimental (Fig. 1A), as expected when directional selection affects linked evolution. variants’ frequency trajectories until ultimately linkage disequi- librium (LD) and the associated additive genetic variance for Results fitness decays (which could occur as a population reaches a new We first analyzed the dataset of Barghi et al. (33), an evolve- optimum and directional selection weakens) (37).
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