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Setter, D.

Publications and source records attributed to Setter, D..

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Sweeps in time: leveraging the joint distribution of branch lengths

Current methods of identifying positively selected regions of the genome are limited by their underlying model in two key ways: the model cannot account for the timing of the adaptive event and the analytic predictions are limited to single nucleotide polymorphisms. Here we develop a tractable method of describing the effect of positive selection on the genealogical histories in the surrounding genome, explicitly modeling both the timing and context of the adaptive event. In addition, our framework allows us to go beyond simple polymorphism data. We are able to leverage information contained in patterns of linked variants, and even with very small sample sizes, our analytic framework has high power to identify historically adaptive regions of the genome and to correctly infer both the time and strength of selection. Finally, we derived the marginal distribution of genealogical branch lengths at a locus affected by selection acting at a linked site. This provides a much-needed link between current theoretical models to recent advances in simulation procedures that have allowed researchers both to examine the evolution of genealogical histories at the level of full chromosomes and build methods that attempt to reconstruct full ancestries from genome sequence data.

evolutionary biology

The impact of global selection on local adaptation and reproductive isolation.

Despite the homogenising effect of strong gene flow between two populations, adaptation under symmetric divergent selection pressures results in partial reproductive isolation: adaptive substitutions act as local barriers to gene flow, and if divergent selection continues unimpeded, this will result in complete reproductive isolation of the two populations, i.e. speciation. However, a key issue in framing the process of speciation as a tension between local adaptation and the homogenising force of gene flow is that the mutation process is blind to changes in the environment and therefore tends to limit adaptation. Here we investigate how globally beneficial mutations (GBMs) affect divergent local adaptation and reproductive isolation. When phenotypic divergence is finite, we show that the presence of GBMs limits local adaptation, generating a persistent genetic load at the loci which contribute to the trait under divergent selection and reducing genome-wide divergence. Furthermore, we show that while GBMs cannot prohibit the process of continuous differentiation, they induce a substantial delay in the genome-wide shutdown of gene flow.

evolutionary biology

VolcanoFinder: genomic scans for adaptive introgression

Recent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method--VolcanoFinder--to detect recent events of adaptive introgression using polymorphism data from the recipient species only.\n\nVolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity.\n\nUsing coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH-RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder.\n\nAuthor summaryThe process by which beneficial alleles are introduced into a species from a closely-related species is termed adaptive introgression. We present an analytically-tractable model for the effects of adaptive introgression on non-adaptive genetic variation in the genomic region surrounding the beneficial allele. The result we describe is a characteristic volcano-shaped pattern of increased variability that arises around the positively-selected site, and we introduce an open-source method VolcanoFinder to detect this signal in genomic data. Importantly, VolcanoFinder is a population-genetic likelihood-based approach, rather than a comparative-genomic approach, and can therefore probe genomic variation data from a single population for footprints of adaptive introgression, even from a priori unknown and possibly extinct donor species.

evolutionary biology