Recombination Modulates How Selection Affects Linked Sites in Drosophila

McGaugh, Suzanne E.; Heil, Caiti Smukowski; Manzano‐Winkler, Brenda; Loewe, Laurence; Goldstein, Steve; Himmel, Tiffany; Noor, Mohamed A. F.

doi:10.1371/journal.pbio.1001422

Cited by 109 publications

(152 citation statements)

References 137 publications

(156 reference statements)

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“…In agreement, we observe no significant relationship between B and ω R estimated along the D. simulans lineage ( ρ = −0.009 based on the default BGS model whereas the other BGS models generate ρ ranging between −0.014 and +0.011; P >0.25 in all cases). A similar result has been obtained in comparisons of local crossover rates and rates of protein evolution between two other closely related Drosophila species, D. pseudoobscura and D. persimilis [88].…”

Section: Resultssupporting

confidence: 82%

Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome

2014

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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.

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Section: Resultssupporting

confidence: 82%

Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome

2014

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“…Some species with strong evidence for selection at linked sites, including Drosophila melanogaster , Drosophila simulans , Caenorhabditis elegans and Caenorhabditis briggsae have lower average meiotic crossover rates 102–104 than do some species with weak signatures, including Arabidopsis thaliana 32 and Saccharomyces cerevisiae 105 . On the other hand, D. pseudoobscura has a relatively high recombination rate 106 but still shows a strong pattern of linked selection, whereas humans exhibit a weaker signature of linked selection despite less crossing over 107 . Our ability to detect linked selection also depends critically on the variance of recombination rate across a genome.…”

Section: Differences In Recombination Profilesmentioning

confidence: 99%

“…Chromosome number and architecture (such as the relative proportions of heterochromatic and euchromatic sequence) contribute to this variance and differ among species. Furthermore, local rates of recombination can evolve rapidly between closely related species 9, 106, 108, 109 .…”

Section: Differences In Recombination Profilesmentioning

confidence: 99%

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Genomic signatures of selection at linked sites: unifying the disparity among species

2013

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Population genetics theory supplies powerful predictions about how natural selection interacts with genetic linkage to sculpt the genomic landscape of nucleotide polymorphism. Both the spread of beneficial mutations and removal of deleterious mutations act to depress polymorphism levels, especially in low-recombination regions. However, empiricists have documented extreme disparities among species. Here we characterize the dominant features that could drive variation in linked selection among species, including roles for selective sweeps being ‘hard’ or ‘soft’, and concealing by demography and genomic confounds. We advocate targeted studies of close relatives to unify our understanding of how selection and linkage interact to shape genome evolution.

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“…Recently, some complications on background selection have been revealed (e.g., [84,85]). To fully understand how our new tests will be impacted by background selection, or more generally the Hill-Robertson interference [86], we will need further studies using simulated data (e.g., [84]) and possibly data on Drosophila genomes (e.g., [85,87-89]).…”

Section: Discussionmentioning

confidence: 99%

Detecting negative selection on recurrent mutations using gene genealogy

2013

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BackgroundWhether or not a mutant allele in a population is under selection is an important issue in population genetics, and various neutrality tests have been invented so far to detect selection. However, detection of negative selection has been notoriously difficult, partly because negatively selected alleles are usually rare in the population and have little impact on either population dynamics or the shape of the gene genealogy. Recently, through studies of genetic disorders and genome-wide analyses, many structural variations were shown to occur recurrently in the population. Such “recurrent mutations” might be revealed as deleterious by exploiting the signal of negative selection in the gene genealogy enhanced by their recurrence.ResultsMotivated by the above idea, we devised two new test statistics. One is the total number of mutants at a recurrently mutating locus among sampled sequences, which is tested conditionally on the number of forward mutations mapped on the sequence genealogy. The other is the size of the most common class of identical-by-descent mutants in the sample, again tested conditionally on the number of forward mutations mapped on the sequence genealogy. To examine the performance of these two tests, we simulated recurrently mutated loci each flanked by sites with neutral single nucleotide polymorphisms (SNPs), with no recombination. Using neutral recurrent mutations as null models, we attempted to detect deleterious recurrent mutations. Our analyses demonstrated high powers of our new tests under constant population size, as well as their moderate power to detect selection in expanding populations. We also devised a new maximum parsimony algorithm that, given the states of the sampled sequences at a recurrently mutating locus and an incompletely resolved genealogy, enumerates mutation histories with a minimum number of mutations while partially resolving genealogical relationships when necessary.ConclusionsWith their considerably high powers to detect negative selection, our new neutrality tests may open new venues for dealing with the population genetics of recurrent mutations as well as help identifying some types of genetic disorders that may have escaped identification by currently existing methods.

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Recombination Modulates How Selection Affects Linked Sites in Drosophila

Abstract: Recombination rate in Drosophila species shapes the impact of selection in the genome and is positively correlated with nucleotide diversity.

Cited by 109 publications

References 137 publications

Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome

Background Selection as Baseline for Nucleotide Variation across the Drosophila Genome

Genomic signatures of selection at linked sites: unifying the disparity among species

Detecting negative selection on recurrent mutations using gene genealogy

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