The Effects on Neutral Variability of Recurrent Selective Sweeps and Background Selection

Abstract

Levels of variability and rates of adaptive evolution may be affected by hitchhiking, the effect of selection on evolution at linked sites. Hitchhiking can be caused either by "selective sweeps" or by background selection, involving the spread of new favorable alleles or the elimination of deleterious mutations, respectively. Recent analyses of population genomic data have fitted models where both these processes act simultaneously, to infer the parameters of selection. Here, we investigate the consequences of relaxing a key assumption of some of these studies, that the time occupied by a selective sweep is negligible compared with the neutral coalescent time. We derive a new expression for the expected level of neutral variability in the presence of recurrent selective sweeps and background selection. We also derive approximate integral expressions for the effects of recurrent selective sweeps. The accuracy of the theoretical predictions was tested against multilocus simulations, with selection, recombination, and mutation parameters that are realistic for Drosophila melanogaster. In the presence of crossing over, there is approximate agreement between the theoretical and simulation results. We show that the observed relationships between the rate of crossing over, and the level of synonymous site diversity and rate of adaptive evolution in Drosophila are probably mainly caused by background selection, whereas selective sweeps and population size changes are needed to produce the observed distortions of the site frequency spectrum.

Inferring Parameters of the Distribution of Fitness Effects of New Mutations When Beneficial Mutations Are Strongly Advantageous and Rare

“…The gene models consisted of five 300bp exons separated by 100bp neutrally evolving introns. The gene models were based on those used by Campos & Charlesworth, (2019) , but unlike that study, I did not model the untranslated regions of genes. Nonsynonymous sites were modeled by drawing the fitness effects for 2/3rds of mutations in exons from a distribution of fitness effects (DFE), while the remaining 1/3 were strictly neutral and used to model synonymous sites.…”

Selective Sweeps Under Dominance and Inbreeding

“…We are interested in calculating (i) the probability P NE that no coalescence or recombination occurs in the sweep phase; (ii) the probability P R;Sw that recombination acts on a lineage to transfer it to the neutral background that is linked to the ancestral allele, assuming that no more than one recombination event occurs per generation (see Campos and Charlesworth (2019) for derivations assuming multiple recombination events). We will go through these probabilities in turn to determine expected pairwise diversity.…”

How Good Are Predictions of the Effects of Selective Sweeps on Levels of Neutral Diversity?

“…The detailed statistics for the results of the computer simulations shown in Figure 3 were provided in Files S2-S3 of Campos and Charlesworth (2019).…”

“…This approximation provides the basis for detecting recent sweeps in the programs SweepFinder (Nielsen et al 2005) and Sweed (Pavlidis et al 2013). It can readily be incorporated into models of recurrent selective sweeps (Barton 2000;Weissman and Barton 2012;Berg and Coop 2015;Elyashiv et al 2016;Campos et al 2017;Campos and Charlesworth 2019), which has stimulated the development of methods for estimating the parameters of recurrent sweeps from population genomic data (Elyashiv et al 2016;Campos et al 2017;Campos and Charlesworth 2019).…”

“…Only hard sweeps will be considered here, although it is straightforward to extend the models to soft sweeps by the approach of Berg and Coop (2015) and Hartfield and Bataillon (2020). The validity of the approximations is tested against computer simulations, including those of Campos and Charlesworth (2019) and Hartfield and Bataillon (2020). For the sake of brevity, these papers will be referred to as CC and HB, respectively.…”