The constant removal of deleterious mutations by natural selection causes a reduction in neutral diversity and efficacy of selection at genetically linked sites (a process called Background Selection, BGS). Population genetic studies, however, often ignore BGS effects when investigating demographic events or the presence of other types of selection. To obtain a more realistic evolutionary expectation that incorporates the unavoidable consequences of deleterious mutations, we generated high-resolution landscapes of variation across the Drosophila melanogaster genome under a BGS scenario independent of polymorphism data. We find that BGS plays a significant role in shaping levels of variation across the entire genome, including long introns and intergenic regions distant from annotated genes. We also find that a very large percentage of the observed variation in diversity across autosomes can be explained by BGS alone, up to 70% across individual chromosome arms at 100-kb scale, thus indicating that BGS predictions can be used as baseline to infer additional types of selection and demographic events. This approach allows detecting several outlier regions with signal of recent adaptive events and selective sweeps. The use of a BGS baseline, however, is particularly appropriate to investigate the presence of balancing selection and our study exposes numerous genomic regions with the predicted signature of higher polymorphism than expected when a BGS context is taken into account. Importantly, we show that these conclusions are robust to the mutation and selection parameters of the BGS model. Finally, analyses of protein evolution together with previous comparisons of genetic maps between Drosophila species, suggest temporally variable recombination landscapes and, thus, local BGS effects that may differ between extant and past phases. Because genome-wide BGS and temporal changes in linkage effects can skew approaches to estimate demographic and selective events, future analyses should incorporate BGS predictions and capture local recombination variation across genomes and along lineages.
The removal of deleterious mutations from natural populations has potential consequences on patterns of variation across genomes. Population genetic analyses, however, often assume that such effects are negligible across recombining regions of species like Drosophila. We use simple models of purifying selection and current knowledge of recombination rates and gene distribution across the genome to obtain a baseline of variation predicted by the constant input and removal of deleterious mutations. We find that purifying selection alone can explain a major fraction of the observed variance in nucleotide diversity across the genome. The use of a baseline of variation predicted by linkage to deleterious mutations as null expectation exposes genomic regions under other selective regimes, including more regions showing the signature of balancing selection than would be evident when using traditional approaches. Our study also indicates that most, if not all, nucleotides across the D. melanogaster genome are significantly influenced by the removal of deleterious mutations, even when located in the middle of highly recombining regions and distant from genes. Additionally, the study of rates of protein evolution confirms previous analyses suggesting that the recombination landscape across the genome has changed in the recent history of D. melanogaster. All these reported factors can skew current analyses designed to capture demographic events or estimate the strength and frequency of adaptive mutations, and illustrate the need for new and more realistic theoretical and modeling approaches to study naturally occurring genetic variation.