Recommendations for improving statistical inference in population genomics

PLoS Biology, Год журнала: 2022, Номер 20(5), С. e3001669 - e3001669

Опубликована: Май 31, 2022

The field of population genomics has grown rapidly in response to the recent advent affordable, large-scale sequencing technologies. As opposed situation during majority 20th century, which development theoretical and statistical genetic insights outpaced generation data they could be applied, genomic are now being produced at a far greater rate than can meaningfully analyzed interpreted. With this wealth come tendency focus on fitting specific (and often rather idiosyncratic) models data, expense careful exploration range possible underlying evolutionary processes. For example, approach directly investigating adaptive evolution each newly sequenced or species neglects fact that thorough characterization ubiquitous nonadaptive processes is prerequisite for accurate inference. We here describe perils these tendencies, present our consensus views current best practices analysis, highlight areas inference theory need further attention. Thereby, we argue importance defining biologically relevant baseline model tuned details new skepticism scrutiny interpreting results, carefully addressable hypotheses uncertainties.

Язык: Английский

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On the prospect of achieving accurate joint estimation of selection with population history

Genome Biology and Evolution, Год журнала: 2022, Номер 14(7)

Опубликована: Июнь 8, 2022

As both natural selection and population history can affect genome-wide patterns of variation, disentangling the contributions each has remained as a major challenge in genetics. We here discuss historical recent progress towards this goal-highlighting theoretical computational challenges that remain to be addressed, well inherent difficulties dealing with model complexity violations-and offer thoughts on potentially fruitful next steps.

Язык: Английский

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How Can We Resolve Lewontin’s Paradox?

Genome Biology and Evolution, Год журнала: 2022, Номер 14(7)

Опубликована: Июнь 23, 2022

Abstract We discuss the genetic, demographic, and selective forces that are likely to be at play in restricting observed levels of DNA sequence variation natural populations a much smaller range values than would expected from distribution census population sizes alone—Lewontin’s Paradox. While several processes have previously been strongly emphasized must involved, including effects direct selection genetic hitchhiking, it seems unlikely they sufficient explain this observation without contributions other factors. highlight potentially important role for less-appreciated contribution size change; specifically, likelihood many species may quite far reaching relatively high equilibrium diversity given their current sizes.

Язык: Английский

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Developing an Evolutionary Baseline Model for Humans: Jointly Inferring Purifying Selection with Population History

Molecular Biology and Evolution, Год журнала: 2023, Номер 40(5)

Опубликована: Май 1, 2023

Abstract Building evolutionarily appropriate baseline models for natural populations is not only important answering fundamental questions in population genetics—including quantifying the relative contributions of adaptive versus nonadaptive processes—but also essential identifying candidate loci experiencing relatively rare and episodic forms selection (e.g., positive or balancing selection). Here, a model was developed human West African ancestry, Yoruba, comprising processes constantly operating on genome (i.e., purifying background selection, size changes, recombination rate heterogeneity, gene conversion). Specifically, to perform joint inference selective effects with demography, an approximate Bayesian approach employed that utilizes decay around functional elements, taking into account genomic architecture. This inferred recent 6-fold growth together distribution fitness skewed towards effectively neutral mutations. Importantly, these results further suggest that, although strong and/or frequent recurrent inconsistent observed data, weak moderate consistent but unidentifiable if rare.

Язык: Английский

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Developing an appropriate evolutionary baseline model for the study of SARS-CoV-2 patient samples

PLoS Pathogens, Год журнала: 2023, Номер 19(4), С. e1011265 - e1011265

Опубликована: Апрель 5, 2023

Over the past 3 years, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has spread through human populations in several waves, resulting a global health crisis. In response, genomic surveillance efforts have proliferated hopes of tracking and anticipating evolution this virus, millions patient isolates now being available public databases. Yet, while there is tremendous focus on identifying newly emerging adaptive viral variants, quantification far from trivial. Specifically, multiple co-occurring interacting evolutionary processes are constantly operation must be jointly considered modeled order to perform accurate inference. We here outline critical individual components such an baseline model—mutation rates, recombination distribution fitness effects, infection dynamics, compartmentalization—and describe current state knowledge pertaining related parameters each SARS-CoV-2. close with series recommendations for future clinical sampling, model construction, statistical analysis.

Язык: Английский

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Evaluating power to detect recurrent selective sweeps under increasingly realistic evolutionary null models

Evolution, Год журнала: 2023, Номер 77(10), С. 2113 - 2127

Опубликована: Июнь 30, 2023

The detection of selective sweeps from population genomic data often relies on the premise that beneficial mutations in question have fixed very near sampling time. As it has been previously shown power to detect a sweep is strongly dependent time since fixation as well strength selection, naturally case strong, recent leave strongest signatures. However, biological reality enter populations at rate, one partially determines mean wait between events and hence their age distribution. An important thus remains about recurrent when they are modeled by realistic mutation rate part distribution fitness effects, opposed single, recent, isolated event purely neutral background more commonly modeled. Here we use forward-in-time simulations study performance used statistics, within context evolutionary baseline models incorporating purifying size change, recombination heterogeneity. Results demonstrate interplay these processes, necessitating caution interpreting selection scans; specifically, false-positive rates excess true-positive across much evaluated parameter space, undetectable unless exceptionally strong.

Язык: Английский

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Admixture has obscured signals of historical hard sweeps in humans

Nature Ecology & Evolution, Год журнала: 2022, Номер 6(12), С. 2003 - 2015

Опубликована: Окт. 31, 2022

The role of natural selection in shaping biological diversity is an area intense interest modern biology. To date, studies positive have primarily relied on genomic datasets from contemporary populations, which are susceptible to confounding factors associated with complex and often unknown aspects population history. In particular, admixture between diverged populations can distort or hide prior events genomes, though this process not explicitly accounted for most despite its apparent ubiquity humans other species. Through analyses ancient human we show that previously reported Holocene-era has masked more than 50 historic hard sweeps European genomes. Our results imply canonical mode probably been underappreciated the evolutionary history suggest our current understanding tempo may be inaccurate.

Язык: Английский

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Population genetic considerations regarding the interpretation of within-patient SARS-CoV-2 polymorphism data

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 16, 2024

Язык: Английский

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Museomics of an extinct European flat oyster population

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Апрель 22, 2025

Abstract Understanding the factors that predispose species and populations to decline extinction is a major challenge of biodiversity research. In present study, we investigated historical population genomics an extinct European oyster ( Ostrea edulis L.) from Wadden Sea collected between 1868 1888, compared it French English sampled at same time. Our museomic results indicate now-extinct was genetically isolated showed signs local adaptation in form Fst outlier loci other two populations. Thus oysters may have been predisposed for because they were not naturally replenished A comparison population-wide genomic diversity hint towards sudden contraction population, possibly being result stronger - or earlier this than others. summary, our exploration hints some potential causes flat Sea, which might led their extinction.

Язык: Английский

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Contrastive sequence signatures between the both sides of a recombination spot reveal an adaptation at PPARD locus from standing variation for pleiotropy since out-of-Africa dispersal

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Апрель 30, 2025

Drug metabolism and transporter genes are a specialized class of involved in absorption, distribution, excretion. They easily present distinct genetic population differentiation vulnerable to natural selection. We initiated study using special panel informative markers such dissected the structure representative Chinese worldwide populations. A distinctive sub-population stratification was discovered extensive Eurasians resulted from divergence at PPARD locus. The contrastive sequence signatures between both sides recombination spot prove selective sweep on this locus for hitchhiking effect. genealogy-based framework demonstrates positive selection acting standing variation exerted moderate pressure Eurasians, drove adaptive allele up high frequency. timing tempo estimations adaptation indicate its onset coincided with early out-of-Africa migration modern humans it lasted over prolonged evolutionary history. phenome-wide association analysis reveals an extended cis-regulation local gene expression pleiotropy implicated variety complex traits. colocalization analyses associations cis-acting traits signify most likely physical capacity, energy metabolism, immune-related involvement, provide prioritization effective casual variants. This work has laid foundation following efforts make full sense biological mechanisms underlying adaptation.

Язык: Английский

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