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  • Oxford University Press (OUP)  (22)
  • 1
    In: Genetics, Oxford University Press (OUP), Vol. 175, No. 2 ( 2007-02-01), p. 795-804
    Abstract: A previous polymorphism survey of the type 2 diabetes gene CAPN10 identified a segment showing an excess of polymorphism levels in all population samples, coinciding with localized breakdown of linkage disequilibrium (LD) in a sample of Hausa from Cameroon, but not in non-African samples. This raised the possibility that a recombination hotspot is present in all populations and we had insufficient power to detect it in the non-African data. To test this possibility, we estimated the crossover rate by sperm typing in five non-African men; these estimates were consistent with the LD decay in the non-African, but not in the Hausa data. Moreover, resequencing the orthologous region in a sample of Western chimpanzees did not show either an excess of polymorphism level or rapid LD decay, suggesting that the processes underlying the patterns observed in humans operated only on the human lineage. These results suggest that a hotspot of recombination has recently arisen in humans and has reached higher frequency in the Hausa than in non-Africans, or that there is no elevation in crossover rate in any human population, and the observed variation results from long-standing balancing selection.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2007
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2012
    In:  Genetics Vol. 192, No. 1 ( 2012-09-01), p. 205-224
    In: Genetics, Oxford University Press (OUP), Vol. 192, No. 1 ( 2012-09-01), p. 205-224
    Abstract: Two major sources of stochasticity in the dynamics of neutral alleles result from resampling of finite populations (genetic drift) and the random genetic background of nearby selected alleles on which the neutral alleles are found (linked selection). There is now good evidence that linked selection plays an important role in shaping polymorphism levels in a number of species. One of the best-investigated models of linked selection is the recurrent full-sweep model, in which newly arisen selected alleles fix rapidly. However, the bulk of selected alleles that sweep into the population may not be destined for rapid fixation. Here we develop a general model of recurrent selective sweeps in a coalescent framework, one that generalizes the recurrent full-sweep model to the case where selected alleles do not sweep to fixation. We show that in a large population, only the initial rapid increase of a selected allele affects the genealogy at partially linked sites, which under fairly general assumptions are unaffected by the subsequent fate of the selected allele. We also apply the theory to a simple model to investigate the impact of recurrent partial sweeps on levels of neutral diversity and find that for a given reduction in diversity, the impact of recurrent partial sweeps on the frequency spectrum at neutral sites is determined primarily by the frequencies rapidly achieved by the selected alleles. Consequently, recurrent sweeps of selected alleles to low frequencies can have a profound effect on levels of diversity but can leave the frequency spectrum relatively unperturbed. In fact, the limiting coalescent model under a high rate of sweeps to low frequency is identical to the standard neutral model. The general model of selective sweeps we describe goes some way toward providing a more flexible framework to describe genomic patterns of diversity than is currently available.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2012
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2010
    In:  Genetics Vol. 186, No. 2 ( 2010-10-01), p. 647-668
    In: Genetics, Oxford University Press (OUP), Vol. 186, No. 2 ( 2010-10-01), p. 647-668
    Abstract: Models for detecting the effect of adaptation on population genomic diversity are often predicated on a single newly arisen mutation sweeping rapidly to fixation. However, a population can also adapt to a new environment by multiple mutations of similar phenotypic effect that arise in parallel, at the same locus or different loci. These mutations can each quickly reach intermediate frequency, preventing any single one from rapidly sweeping to fixation globally, leading to a “soft” sweep in the population. Here we study various models of parallel mutation in a continuous, geographically spread population adapting to a global selection pressure. The slow geographic spread of a selected allele due to limited dispersal can allow other selected alleles to arise and start to spread elsewhere in the species range. When these different selected alleles meet, their spread can slow dramatically and so initially form a geographic patchwork, a random tessellation, which could be mistaken for a signal of local adaptation. This spatial tessellation will dissipate over time due to mixing by migration, leaving a set of partial sweeps within the global population. We show that the spatial tessellation initially formed by mutational types is closely connected to Poisson process models of crystallization, which we extend. We find that the probability of parallel mutation and the spatial scale on which parallel mutation occurs are captured by a single compound parameter, a characteristic length, which reflects the expected distance a spreading allele travels before it encounters a different spreading allele. This characteristic length depends on the mutation rate, the dispersal parameter, the effective local density of individuals, and to a much lesser extent the strength of selection. While our knowledge of these parameters is poor, we argue that even in widely dispersing species, such parallel geographic sweeps may be surprisingly common. Thus, we predict that as more data become available, many more examples of intraspecies parallel adaptation will be uncovered.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2010
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  • 4
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2017
    In:  Genetics Vol. 205, No. 3 ( 2017-03-01), p. 1335-1351
    In: Genetics, Oxford University Press (OUP), Vol. 205, No. 3 ( 2017-03-01), p. 1335-1351
    Abstract: Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These identity-by-descent (IBD) blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulas for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite-likelihood approach to fit these formulas. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block-sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the Population Reference Sample data set. We show that ancestry diffusing with a rate of σ≈50−−100 km/gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2017
    In:  Genetics Vol. 207, No. 4 ( 2017-12-01), p. 1591-1619
    In: Genetics, Oxford University Press (OUP), Vol. 207, No. 4 ( 2017-12-01), p. 1591-1619
    Abstract: Cases of convergent adaptation demonstrate the power of natural selection and can be used as an important tool for studying the molecular and ecological.. Geographically separated populations can convergently adapt to the same selection pressure. Convergent evolution at the level of a gene may arise via three distinct modes. The selected alleles can (1) have multiple independent mutational origins, (2) be shared due to shared ancestral standing variation, or (3) spread throughout subpopulations via gene flow. We present a model-based, statistical approach that utilizes genomic data to detect cases of convergent adaptation at the genetic level, identify the loci involved and distinguish among these modes. To understand the impact of convergent positive selection on neutral diversity at linked loci, we make use of the fact that hitchhiking can be modeled as an increase in the variance in neutral allele frequencies around a selected site within a population. We build on coalescent theory to show how shared hitchhiking events between subpopulations act to increase covariance in allele frequencies between subpopulations at loci near the selected site, and extend this theory under different models of migration and selection on the same standing variation. We incorporate this hitchhiking effect into a multivariate normal model of allele frequencies that also accounts for population structure. Based on this theory, we present a composite-likelihood-based approach that utilizes genomic data to identify loci involved in convergence, and distinguishes among alternate modes of convergent adaptation. We illustrate our method on genome-wide polymorphism data from two distinct cases of convergent adaptation. First, we investigate the adaptation for copper toxicity tolerance in two populations of the common yellow monkey flower, Mimulus guttatus. We show that selection has occurred on an allele that has been standing in these populations prior to the onset of copper mining in this region. Lastly, we apply our method to data from four populations of the killifish, Fundulus heteroclitus, that show very rapid convergent adaptation for tolerance to industrial pollutants. Here, we identify a single locus at which both independent mutation events and selection on an allele shared via gene flow, either slightly before or during selection, play a role in adaptation across the species’ range.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2013
    In:  Genetics Vol. 195, No. 1 ( 2013-09-01), p. 205-220
    In: Genetics, Oxford University Press (OUP), Vol. 195, No. 1 ( 2013-09-01), p. 205-220
    Abstract: Comparing allele frequencies among populations that differ in environment has long been a tool for detecting loci involved in local adaptation. However, such analyses are complicated by an imperfect knowledge of population allele frequencies and neutral correlations of allele frequencies among populations due to shared population history and gene flow. Here we develop a set of methods to robustly test for unusual allele frequency patterns and correlations between environmental variables and allele frequencies while accounting for these complications based on a Bayesian model previously implemented in the software Bayenv. Using this model, we calculate a set of “standardized allele frequencies” that allows investigators to apply tests of their choice to multiple populations while accounting for sampling and covariance due to population history. We illustrate this first by showing that these standardized frequencies can be used to detect nonparametric correlations with environmental variables; these correlations are also less prone to spurious results due to outlier populations. We then demonstrate how these standardized allele frequencies can be used to construct a test to detect SNPs that deviate strongly from neutral population structure. This test is conceptually related to FST and is shown to be more powerful, as we account for population history. We also extend the model to next-generation sequencing of population pools—a cost-efficient way to estimate population allele frequencies, but one that introduces an additional level of sampling noise. The utility of these methods is demonstrated in simulations and by reanalyzing human SNP data from the Human Genome Diversity Panel populations and pooled next-generation sequencing data from Atlantic herring. An implementation of our method is available from http://gcbias.org.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2015
    In:  Genetics Vol. 201, No. 1 ( 2015-09-01), p. 243-261
    In: Genetics, Oxford University Press (OUP), Vol. 201, No. 1 ( 2015-09-01), p. 243-261
    Abstract: Recent genomic studies have highlighted the important role of admixture in shaping genome-wide patterns of diversity. Past admixture leaves a population genomic signature of linkage disequilibrium (LD), reflecting the mixing of parental chromosomes by segregation and recombination. These patterns of LD can be used to infer the timing of admixture, but the results of inference can depend strongly on the assumed demographic model. Here, we introduce a theoretical framework for modeling patterns of LD in a geographic contact zone where two differentiated populations have come into contact and are mixing by diffusive local migration. Assuming that this secondary contact is recent enough that genetic drift can be ignored, we derive expressions for the expected LD and admixture tract lengths across geographic space as a function of the age of the contact zone and the dispersal distance of individuals. We develop an approach to infer age of contact zones, using population genomic data from multiple spatially sampled populations by fitting our model to the decay of LD with recombination distance. To demonstrate an application of our model, we use our approach to explore the fit of a geographic contact zone model to three human genomic data sets from populations in Indonesia, Central Asia, and India and compare our results to inference under different demographic models. We obtain substantially different results from those of the commonly used model of panmictic admixture, highlighting the sensitivity of admixture timing results to the choice of demographic model.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2015
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  • 8
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2019
    In:  Genetics Vol. 211, No. 3 ( 2019-03-01), p. 989-1004
    In: Genetics, Oxford University Press (OUP), Vol. 211, No. 3 ( 2019-03-01), p. 989-1004
    Abstract: Adaptation in quantitative traits often occurs through subtle shifts in allele frequencies at many loci—a process called polygenic adaptation. While a number of methods have been developed to detect polygenic adaptation in human populations, we lack clear strategies for doing so in many other systems. In particular, there is an opportunity to develop new methods that leverage datasets with genomic data and common garden trait measurements to systematically detect the quantitative traits important for adaptation. Here, we develop methods that do just this, using principal components of the relatedness matrix to detect excess divergence consistent with polygenic adaptation, and using a conditional test to control for confounding effects due to population structure. We apply these methods to inbred maize lines from the United States Department of Agriculture germplasm pool and maize landraces from Europe. Ultimately, these methods can be applied to additional domesticated and wild species to give us a broader picture of the specific traits that contribute to adaptation and the overall importance of polygenic adaptation in shaping quantitative trait variation.
    Type of Medium: Online Resource
    ISSN: 1943-2631
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2019
    detail.hit.zdb_id: 1477228-0
    SSG: 12
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Molecular Biology and Evolution Vol. 35, No. 4 ( 2018-04-01), p. 1003-1017
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 35, No. 4 ( 2018-04-01), p. 1003-1017
    Abstract: The haplotypes of a beneficial allele carry information about its history that can shed light on its age and the putative cause for its increase in frequency. Specifically, the signature of an allele’s age is contained in the pattern of variation that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to estimate the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans.
    Type of Medium: Online Resource
    ISSN: 0737-4038 , 1537-1719
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2024221-9
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2008
    In:  Molecular Biology and Evolution Vol. 25, No. 7 ( 2008-7), p. 1257-1259
    In: Molecular Biology and Evolution, Oxford University Press (OUP), Vol. 25, No. 7 ( 2008-7), p. 1257-1259
    Type of Medium: Online Resource
    ISSN: 1537-1719 , 0737-4038
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2008
    detail.hit.zdb_id: 2024221-9
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