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Gene clusters are genomic loci that contain multiple genes that are functionally and genetically linked. Gene clusters collectively encode diverse functions, including small molecule biosynthesis, nutrient assimilation, metabolite degradation, and production of proteins essential for growth and development. Identifying gene clusters is a powerful tool for small molecule discovery and provides insight into the ecology and evolution of organisms. Current detection algorithms focus on canonical 'core' biosynthetic functions many gene clusters encode, while overlooking uncommon or unknown cluster classes. These overlooked clusters are a potential source of novel natural products and comprise an untold portion of overall gene cluster repertoires. Unbiased, function-agnostic detection algorithms therefore provide an opportunity to reveal novel classes of gene clusters and more precisely define genome organization. We present CLOCI (Co-occurrence Locus and Orthologous Cluster Identifier), an algorithm that identifies gene clusters using multiple proxies of selection for coordinated gene evolution. Our approach generalizes gene cluster detection and gene cluster family circumscription, improves detection of multiple known functional classes, and unveils non-canonical gene clusters. CLOCI is suitable for genome-enabled small molecule mining, and presents an easily tunable approach for delineating gene cluster families and homologous loci.
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Many questions in evolutionary biology require the specification of a phylogeny for downstream phylogenetic analyses. However, with the increasingly widespread availability of genomic data, phylogenetic studies are often confronted with conflicting signal in the form of genomic heterogeneity and incongruence between gene trees and the species tree. This raises the question of determining what data and phylogeny should be used in downstream analyses, and to what extent the choice of phylogeny (e.g., gene trees versus species trees) impacts the analyses and their outcomes. In this paper, we study this question in the realm of phylogenetic diversity indices, which provide ways to prioritize species for conservation based on their relative evolutionary isolation on a phylogeny, and are thus one example of downstream phylogenetic analyses. We use the Fair Proportion (FP) index, also known as the evolutionary distinctiveness score, and explore the variability in species rankings based on gene trees as compared to the species tree for several empirical data sets. Our results indicate that prioritization rankings among species vary greatly depending on the underlying phylogeny, suggesting that the choice of phylogeny is a major influence in assessing phylogenetic diversity in a conservation setting. While we use phylogenetic diversity conservation as an example, we suspect that other types of downstream phylogenetic analyses such as ancestral state reconstruction are similarly affected by genomic heterogeneity and incongruence. Our aim is thus to raise awareness of this issue and inspire new research on which evolutionary information (species trees, gene trees, or a combination of both) should form the basis for analyses in these settings.
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Filogenia , Evolução Molecular , Animais , Modelos GenéticosRESUMO
Methods based on the multi-species coalescent have been widely used in phylogenetic tree estimation using genome-scale DNA sequence data to understand the underlying evolutionary relationship between the sampled species. Evolutionary processes such as hybridization, which creates new species through interbreeding between two different species, necessitate inferring a species network instead of a species tree. A species tree is strictly bifurcating and thus fails to incorporate hybridization events which require an internal node of degree three. Hence, it is crucial to decide whether a tree or network analysis should be performed given a DNA sequence data set, a decision that is based on the presence of hybrid species in the sampled species. Although many methods have been proposed for hybridization detection, it is rare to find a technique that does so globally while considering a data generation mechanism that allows both hybridization and incomplete lineage sorting. In this paper, we consider hybridization and coalescence in a unified framework and propose a new test that can detect whether there are any hybrid species in a set of species of arbitrary size. Based on this global test of hybridization, one can decide whether a tree or network analysis is appropriate for a given data set.
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Evolução Biológica , Hibridização Genética , Filogenia , Modelos GenéticosRESUMO
Study of the genome of the SARS-CoV-2 virus, particularly with regard to understanding evolution of the virus, is crucial for managing the COVID-19 pandemic. To this end, we sample viral genomes from the GISAID repository and use several of the maximum likelihood approaches implemented in PAML, a collection of open source programs for phylogenetic analyses of DNA and protein sequences, to assess evidence for positive selection in the protein-coding regions of the SARS-CoV-2 genome. Across all major variants identified by June 2021, we find limited evidence for positive selection. In particular, we identify positive selection in a small proportion of sites (5-15%) in the protein-coding region of the spike protein across variants. Most other variants did not show a strong signal for positive selection overall, though there were indications of positive selection in the Delta and Kappa variants for the nucleocapsid protein. We additionally use a forward selection procedure to fit a model that allows branch-specific estimates of selection along a phylogeny relating the variants, and find that there is variation in the selective pressure across variants for the spike protein. Our results highlight the utility of computational approaches for identifying genomic regions under selection.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/genética , Funções Verossimilhança , Pandemias , Filogenia , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
The effect of selection acting on regions of the genome on the accuracy of species-level phylogenetic inference using methods that do not explicitly model selection is an open question that is relevant to most, if not all, phylogenomic studies. To address this, we derive a mathematical approximation to the Wright-Fisher model with mutation and selection in the limit as the population size becomes large. In contrast to previous approximations based on diffusion processes, our approximation can be used to study the distribution of coalescent times for an arbitrary number of lineages, allowing calculation of the probability distribution of gene genealogies under the coalescent model. We use these calculations to show that direct selection at strengths typically encountered in practice has only a small effect on the distribution of coalescent times, and hence on the distribution of gene trees. This implies that many coalescent-based methods for estimating the species tree topology will be robust to the presence of selection in a subset of the underlying genes. Selection will, however, bias the estimation of speciation times, causing them to underestimate the true speciation times. Our model captures the effects of selection on the genealogies that generate the observed sequence data, but does not model selective pressures that act only on the subsequent sequences or that negatively impact gene tree estimation.
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Especiação Genética , Modelos Genéticos , Filogenia , Probabilidade , MutaçãoRESUMO
Although the role of evolutionary process in cancer progression is widely accepted, increasing attention is being given to the evolutionary mechanisms that can lead to differences in clinical outcome. Recent studies suggest that the temporal order in which somatic mutations accumulate during cancer progression is important. Single-cell sequencing (SCS) provides a unique opportunity to examine the effect that the mutation order has on cancer progression and treatment effect. However, the error rates associated with single-cell sequencing are known to be high, which greatly complicates the task. We propose a novel method for inferring the order in which somatic mutations arise within an individual tumor using noisy data from single-cell sequencing. Our method incorporates models at two levels in that the evolutionary process of somatic mutation within the tumor is modeled along with the technical errors that arise from the single-cell sequencing data collection process. Through analyses of simulations across a wide range of realistic scenarios, we show that our method substantially outperforms existing approaches for identifying mutation order. Most importantly, our method provides a unique means to capture and quantify the uncertainty in the inferred mutation order along a given phylogeny. We illustrate our method by analyzing data from colorectal and prostate cancer patients, in which our method strengthens previously reported mutation orders. Our work is an important step towards producing meaningful prediction of mutation order with high accuracy and measuring the uncertainty of predicted mutation order in cancer patients, with the potential to lead to new insights about the evolutionary trajectories of cancer.
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Neoplasias , Humanos , Filogenia , Neoplasias/genética , Neoplasias/patologia , Processos Neoplásicos , Mutação/genética , Evolução BiológicaRESUMO
Phylogenetic diversity indices such as the Fair Proportion (FP) index are frequently discussed as prioritization criteria in biodiversity conservation. They rank species according to their contribution to overall diversity by taking into account the unique and shared evolutionary history of each species as indicated by its placement in an underlying phylogenetic tree. Traditionally, phylogenetic trees were inferred from single genes and the resulting gene trees were assumed to be a valid estimate for the species tree, i.e., the "true" evolutionary history of the species under consideration. However, nowadays it is common to sequence whole genomes of hundreds or thousands of genes, and it is often the case that conflicting genealogical histories exist in different genes throughout the genome, resulting in discordance between individual gene trees and the species tree. Here, we analyze the effects of gene and species tree discordance on prioritization decisions based on the FP index. In particular, we consider the ranking order of taxa induced by (i) The FP index on a species tree, and (ii) The expected FP index across all gene tree histories associated with the species tree. On the one hand, we show that for particular tree shapes, the two rankings always coincide. On the other hand, we show that for all leaf numbers greater than or equal to five, there exist species trees for which the two rankings differ. Finally, we illustrate the variability in the rankings obtained from the FP index across different gene tree and species tree estimates for an empirical multilocus mammal data set.
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FilogeniaRESUMO
MOTIVATION: The multispecies coalescent model is now widely accepted as an effective model for incorporating variation in the evolutionary histories of individual genes into methods for phylogenetic inference from genome-scale data. However, because model-based analysis under the coalescent can be computationally expensive for large datasets, a variety of inferential frameworks and corresponding algorithms have been proposed for estimation of species-level phylogenies and associated parameters, including speciation times and effective population sizes. RESULTS: We consider the problem of estimating the timing of speciation events along a phylogeny in a coalescent framework. We propose a maximum a posteriori estimator based on composite likelihood (MAPCL) for inferring these speciation times under a model of DNA sequence evolution for which exact site-pattern probabilities can be computed under the assumption of a constant θ throughout the species tree. We demonstrate that the MAPCL estimates are statistically consistent and asymptotically normally distributed, and we show how this result can be used to estimate their asymptotic variance. We also provide a more computationally efficient estimator of the asymptotic variance based on the non-parametric bootstrap. We evaluate the performance of our method using simulation and by application to an empirical dataset for gibbons. AVAILABILITY AND IMPLEMENTATION: The method has been implemented in the PAUP* program, freely available at https://paup.phylosolutions.com for Macintosh, Windows and Linux operating systems. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
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Algoritmos , Software , Filogenia , Simulação por Computador , Probabilidade , Modelos Genéticos , Especiação GenéticaRESUMO
The evolutionary relationships among organisms have traditionally been represented using rooted phylogenetic trees. However, due to reticulate processes such as hybridization or lateral gene transfer, evolution cannot always be adequately represented by a phylogenetic tree, and rooted phylogenetic networks that describe such complex processes have been introduced as a generalization of rooted phylogenetic trees. In fact, estimating rooted phylogenetic networks from genomic sequence data and analyzing their structural properties is one of the most important tasks in contemporary phylogenetics. Over the last two decades, several subclasses of rooted phylogenetic networks (characterized by certain structural constraints) have been introduced in the literature, either to model specific biological phenomena or to enable tractable mathematical and computational analyses. In the present manuscript, we provide a thorough review of these network classes, as well as provide a biological interpretation of the structural constraints underlying these networks where possible. In addition, we discuss how imposing structural constraints on the network topology can be used to address the scalability and identifiability challenges faced in the estimation of phylogenetic networks from empirical data.
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Transferência Genética Horizontal , Hibridização Genética , Algoritmos , Evolução Biológica , Modelos Genéticos , FilogeniaRESUMO
Whereas DNA viruses are known to be abundant, diverse, and commonly key ecosystem players, RNA viruses are insufficiently studied outside disease settings. In this study, we analyzed ≈28 terabases of Global Ocean RNA sequences to expand Earth's RNA virus catalogs and their taxonomy, investigate their evolutionary origins, and assess their marine biogeography from pole to pole. Using new approaches to optimize discovery and classification, we identified RNA viruses that necessitate substantive revisions of taxonomy (doubling phyla and adding >50% new classes) and evolutionary understanding. "Species"-rank abundance determination revealed that viruses of the new phyla "Taraviricota," a missing link in early RNA virus evolution, and "Arctiviricota" are widespread and dominant in the oceans. These efforts provide foundational knowledge critical to integrating RNA viruses into ecological and epidemiological models.
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Genoma Viral , Vírus de RNA , Vírus , Evolução Biológica , Ecossistema , Oceanos e Mares , Filogenia , RNA , Vírus de RNA/genética , Viroma/genética , Vírus/genéticaRESUMO
A phylogenetic model of sequence evolution for a set of n taxa is a collection of probability distributions on the 4 n possible site patterns that may be observed in their aligned DNA sequences. For a four-taxon model, one can arrange the entries of these probability distributions into three flattening matrices that correspond to the three different unrooted leaf-labeled four-leaf trees, or quartet trees. The flattening matrix corresponding to the tree parameter of the model is known to satisfy certain rank conditions. Methods such as ErikSVD and SVDQuartets take advantage of this observation by applying singular value decomposition to flattening matrices consisting of empirical data. Each possible quartet is assigned an "SVD score" based on how close the flattening is to the set of matrices of the predicted rank. When choosing among possible quartets, the one with the lowest score is inferred to be the phylogeny of the four taxa under consideration. Since an n-leaf phylogenetic tree is determined by its quartets, this approach can be generalized to infer larger phylogenies. In this article, we explore using the SVD score as a test statistic to test whether phylogenetic data were generated by a particular quartet tree. To do so, we use several results to approximate the distribution of the SVD score and to give upper bounds on the p-value of the associated hypothesis tests. We also apply these hypothesis tests to simulated phylogenetic data and discuss the implications for interpreting SVD scores in rank-based inference methods.
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Inference of the evolutionary histories of species, commonly represented by a species tree, is complicated by the divergent evolutionary history of different parts of the genome. Different loci on the genome can have different histories from the underlying species tree (and each other) due to processes such as incomplete lineage sorting (ILS), gene duplication and loss, and horizontal gene transfer. The multispecies coalescent is a commonly used model for performing inference on species and gene trees in the presence of ILS. This paper introduces Lily-T and Lily-Q, two new methods for species tree inference under the multispecies coalescent. We then compare them to two frequently used methods, SVDQuartets and ASTRAL, using simulated and empirical data. Both methods generally showed improvement over SVDQuartets, and Lily-Q was superior to Lily-T for most simulation settings. The comparison to ASTRAL was more mixed-Lily-Q tended to be better than ASTRAL when the length of recombination-free loci was short, when the coalescent population parameter [Formula: see text] was small, or when the internal branch lengths were longer.
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Especiação Genética , Conceitos Matemáticos , Teorema de Bayes , Simulação por Computador , Modelos Genéticos , FilogeniaRESUMO
Despite the recent availability of large-scale genomic data for many individuals, few methods for phylogenetic inference are both computationally efficient and highly accurate for trees with hundreds of taxa. Model-based methods such as those developed in the maximum likelihood and Bayesian frameworks are especially time-consuming, as they involve both computationally intensive calculations on fixed phylogenies and searches through the space of possible phylogenies, and they are known to scale poorly with the addition of taxa. Here, we propose a fast approximation to the maximum likelihood estimator that directly uses continuous trait data, such as allele frequency data. The approximation works by first computing the maximum likelihood estimates of some internal branch lengths, and then inferring the tree-topology using these estimates. Our approach is more computationally efficient than existing methods for such data while still achieving comparable accuracy. This method is innovative in its use of the mathematical properties of tree-topologies for inference, and thus serves as a useful addition to the collection of methods available for estimating phylogenies from continuous trait data.
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Funções Verossimilhança , Filogenia , Teorema de Bayes , Frequência do Gene , Humanos , Fenótipo , Reprodutibilidade dos Testes , Projetos de PesquisaRESUMO
Interspecific hybridization is an important evolutionary phenomenon that generates genetic variability in a population and fosters species diversity in nature. The availability of large genome scale data sets has revolutionized hybridization studies to shift from the observation of the presence or absence of hybrids to the investigation of the genomic constitution of hybrids and their genome-specific evolutionary dynamics. Although a handful of methods have been proposed in an attempt to identify hybrids, accurate detection of hybridization from genomic data remains a challenging task. In addition to methods that infer phylogenetic networks or that utilize pairwise divergence, site pattern frequency based and population genetic clustering approaches are popularly used in practice, though the performance of these methods under different hybridization scenarios has not been extensively examined. Here, we use simulated data to comparatively evaluate the performance of four tools that are commonly used to infer hybridization events: the site pattern frequency based methods HyDe and the $D$-statistic (i.e., the ABBA-BABA test) and the population clustering approaches structure and ADMIXTURE. We consider single hybridization scenarios that vary in the time of hybridization and the amount of incomplete lineage sorting (ILS) for different proportions of parental contributions ($\gamma$); introgressive hybridization; multiple hybridization scenarios; and a mixture of ancestral and recent hybridization scenarios. We focus on the statistical power to detect hybridization and the false discovery rate (FDR) for comparisons of the $D$-statistic and HyDe, and the accuracy of the estimates of $\gamma$ as measured by the mean squared error for HyDe, structure, and ADMIXTURE. Both HyDe and the $D$-statistic are powerful for detecting hybridization in all scenarios except those with high ILS, although the $D$-statistic often has an unacceptably high FDR. The estimates of $\gamma$ in HyDe are impressively robust and accurate whereas structure and ADMIXTURE sometimes fail to identify hybrids, particularly when the proportional parental contributions are asymmetric (i.e., when $\gamma$ is close to 0). Moreover, the posterior distribution estimated using structure exhibits multimodality in many scenarios, making interpretation difficult. Our results provide guidance in selecting appropriate methods for identifying hybrid populations from genomic data. [ABBA-BABA test; ADMIXTURE; hybridization; HyDe; introgression; Patterson's $D$-statistic; Structure.].
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Genoma , Hibridização Genética , Genética Populacional , Genômica , FilogeniaRESUMO
Numerous methods for inferring species-level phylogenies under the coalescent model have been proposed within the last 20 years, and debates continue about the relative strengths and weaknesses of these methods. One desirable property of a phylogenetic estimator is that of statistical consistency, which means intuitively that as more data are collected, the probability that the estimated tree has the same topology as the true tree goes to 1. To date, consistency results for species tree inference under the multispecies coalescent (MSC) have been derived only for summary statistics methods, such as ASTRAL and MP-EST. These methods have been found to be consistent given true gene trees but may be inconsistent when gene trees are estimated from data for loci of finite length. Here, we consider the question of statistical consistency for four taxa for SVDQuartets for general data types, as well as for the maximum likelihood (ML) method in the case in which the data are a collection of sites generated under the MSC model such that the sites are conditionally independent given the species tree (we call these data coalescent independent sites [CIS] data). We show that SVDQuartets is statistically consistent for all data types (i.e., for both CIS data and for multilocus data), and we derive its rate of convergence. We additionally show that ML is consistent for CIS data under the JC69 model and discuss why a proof for the more general multilocus case is difficult. Finally, we compare the performance of ML and SDVQuartets using simulation for both data types. [Consistency; gene tree; maximum likelihood; multilocus data; hylogenetic inference; species tree; SVDQuartets.].
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Especiação Genética , Modelos Genéticos , Simulação por Computador , Filogenia , ProbabilidadeRESUMO
BACKGROUND: Coalescent-based species tree inference has become widely used in the analysis of genome-scale multilocus and SNP datasets when the goal is inference of a species-level phylogeny. However, numerous evolutionary processes are known to violate the assumptions of a coalescence-only model and complicate inference of the species tree. One such process is hybrid speciation, in which a species shares its ancestry with two distinct species. Although many methods have been proposed to detect hybrid speciation, only a few have considered both hybridization and coalescence in a unified framework, and these are generally limited to the setting in which putative hybrid species must be identified in advance. RESULTS: Here we propose a method that can examine genome-scale data for a large number of taxa and detect those taxa that may have arisen via hybridization, as well as their potential "parental" taxa. The method is based on a model that considers both coalescence and hybridization together, and uses phylogenetic invariants to construct a test that scales well in terms of computational time for both the number of taxa and the amount of sequence data. We test the method using simulated data for up 20 taxa and 100,000bp, and find that the method accurately identifies both recent and ancient hybrid species in less than 30 s. We apply the method to two empirical datasets, one composed of Sistrurus rattlesnakes for which hybrid speciation is not supported by previous work, and one consisting of several species of Heliconius butterflies for which some evidence of hybrid speciation has been previously found. CONCLUSIONS: The proposed method is powerful for detecting hybridization for both recent and ancient hybridization events. The computations required can be carried out rapidly for a large number of sequences using genome-scale data, and the method is appropriate for both SNP and multilocus data.
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Bases de Dados Genéticas , Genômica , Hibridização Genética , Modelos Genéticos , Animais , Borboletas/genética , Simulação por Computador , Crotalus/genética , Especiação Genética , Filogenia , Especificidade da EspécieRESUMO
Plant viral diseases are one of the major limitations in legume production within sub-Saharan Africa (SSA), as they account for up to 100% in production losses within smallholder farms. In this study, field surveys were conducted in the western highlands of Kenya with viral symptomatic leaf samples collected. Subsequently, next-generation sequencing was carried out to gain insights into the molecular evolution and evolutionary relationships of Bean common mosaic necrosis virus (BCMNV) and Cowpea aphid-borne mosaic virus (CABMV) present within symptomatic common bean and cowpea. Eleven near-complete genomes of BCMNV and two for CABMV were obtained from western Kenya. Bayesian phylogenomic analysis and tests for differential selection pressure within sites and across tree branches of the viral genomes were carried out. Three well-supported clades in BCMNV and one supported clade for CABMNV were resolved and in agreement with individual gene trees. Selection pressure analysis within sites and across phylogenetic branches suggested both viruses were evolving independently, but under strong purifying selection, with a slow evolutionary rate. These findings provide valuable insights on the evolution of BCMNV and CABMV genomes and their relationship to other viral genomes globally. The results will contribute greatly to the knowledge gap involving the phylogenomic relationship of these viruses, particularly for CABMV, for which there are few genome sequences available, and inform the current breeding efforts towards resistance for BCMNV and CABMV.
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Coalescent models of evolution account for incomplete lineage sorting by specifying a species tree parameter which determines a distribution on gene trees, and consequently, a site pattern probability distribution. It has been shown that the unrooted topology of the species tree parameter of the multispecies coalescent is generically identifiable, and a reconstruction method called SVDQuartets has been developed to infer this topology. In this paper, we describe a modified multispecies coalescent model that allows for varying effective population size and violations of the molecular clock. We show that the unrooted topology of the species tree parameter for these models is generically identifiable and that SVDQuartets can still be used to infer this topology.
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Modelos Genéticos , Filogenia , Biologia Computacional , Simulação por Computador , Evolução Molecular , Especiação Genética , Conceitos Matemáticos , Modelos Estatísticos , ProbabilidadeRESUMO
The increasing availability of population-level allele frequency data across one or more related populations necessitates the development of methods that can efficiently estimate population genetics parameters, such as the strength of selection acting on the population(s), from such data. Existing methods for this problem in the setting of the Wright-Fisher diffusion model are primarily likelihood-based, and rely on numerical approximation for likelihood computation and on bootstrapping for assessment of variability in the resulting estimates, requiring extensive computation. Recent work has provided a method for obtaining exact samples from general Wright-Fisher diffusion processes, enabling the development of methods for Bayesian estimation in this setting. We develop and implement a Bayesian method for estimating the strength of selection based on the Wright-Fisher diffusion for data sampled at a single time point. The method utilizes the latest algorithms for exact sampling to devise a Markov chain Monte Carlo procedure to draw samples from the joint posterior distribution of the selection coefficient and the allele frequencies. We demonstrate that when assumptions about the initial allele frequencies are accurate the method performs well for both simulated data and for an empirical data set on hypoxia in flies, where we find evidence for strong positive selection in a region of chromosome 2L previously identified. We discuss possible extensions of our method to the more general settings commonly encountered in practice, highlighting the advantages of Bayesian approaches to inference in this setting.