Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection

Johri, Parul; Charlesworth, Brian; Jensen, Jeffrey D.

doi:10.1534/genetics.119.303002

Cited by 135 publications

(229 citation statements)

References 97 publications

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“…2018). Recently, Johri et al . (2020) proposed using approximate Bayesian computation for joint inference of demography and purifying selection, which could lead to more appropriate null models for the detection of loci involved in adaptation.…”

Section: Discussionmentioning

confidence: 99%

Power and limits of selection genome scans on temporal data from a selfing population

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Becheler

Ronfort

et al. 2020

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Tracking genetic changes of populations through time allows a more direct study of the evolutionary processes acting on the population than a single contemporary sample. Several statistical methods have been developed to characterize the demography and selection from temporal population genetic data. However, these methods are usually developed under the assumption of outcrossing reproduction and might not be applicable when there is substantial selfing in the population. Here, we focus on a method to detect loci under selection based on a genome scan of temporal differentiation, adapting it to the particularities of selfing populations. Selfing reduces the effective recombination rate and can extend hitch-hiking effects to the whole genome, erasing any local signal of selection on a genome scan. Therefore, selfing is expected to reduce the power of the method. By means of simulations, we evaluate the performance of the method under scenarios of adaptation from new mutations or standing variation at different rates of selfing. We find that the detection of loci under selection in predominantly selfing populations remains challenging even with the adapted method. Still, selective sweeps from standing variation on predominantly selfing populations can leave some signal of selection around the selected site thanks to historical recombination before the sweep. Under this scenario, ancestral advantageous alleles at low frequency leave the strongest local signal, while new advantageous mutations leave no local footprint of the sweep. selective sweep | neutrality test | temporal differentiation | Medicago truncatulaCorrespondence: UMR CBGP, INRAE, Centre de Biologie pour la Gestion des Populations; 755 avenue du campus Agropolis; CS30016; 34988 Montferrier-sur-Lez cedex (France)

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Section: Discussionmentioning

confidence: 99%

Power and limits of selection genome scans on temporal data from a selfing population

Navascués

Becheler

Ronfort

et al. 2020

Preprint

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“…Priors on ancestral and current population sizes were drawn from a uniform distribution between 10 5 -10 7 diploid individuals, while the time of change was fixed at 10 6 608 (~Ne) generations. In order to simulate functional regions, 94 single-exon genes, as described in Johri et al (2020) and provided in https://github.com/paruljohri/BGS_Demography_DFE/blob/master/DPGP3_data.zip, were simulated with recombination rates specific to those exons (https://petrov.stanford.edu/cgibin/recombination-rates_updateR5.pl) (Fiston-Lavier et al 2010;Comeron et al 2012). Mutation rates were assumed to be fixed at 3 × 10 -9 per site per generation (Keightley et al 2009;Keightley et al 2014).…”

Section: Performing Inference By Approximate Bayesian Computation (Abc)mentioning

confidence: 99%

The impact of purifying and background selection on the inference of population history: problems and prospects

Johri

Riall

Becher

et al. 2020

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ABSTRACTCurrent procedures for inferring population history are generally performed under the assumption of complete neutrality - that is, by neglecting both direct selection and the effects of selection on linked sites. We here examine how the presence of direct purifying and background selection may bias demographic inference by evaluating two commonly-used methods (MSMC and fastsimcoal2), specifically studying how the underlying shape of the distribution of fitness effects (DFE) and the fraction of directly selected sites interact with demographic parameter estimation. The results show that, even after masking functional genomic regions, background selection effects may result in the mis-inference of population growth under models of both constant population size as well as decline. This effect is amplified as the strength of purifying selection and the density of directly selected sites increases, as indicated by the distortion of the site frequency spectrum and levels of nucleotide diversity at linked neutral sites. We also show how simulated changes in background selection effects caused by population size changes can be predicted analytically. We propose a potential method for correcting for the mis-inference of population growth caused by selection. By treating the DFE as a nuisance parameter and averaging across all potential realizations, we demonstrate that even directly selected sites may be used to infer demographic histories with reasonable accuracy.

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“…In addition, we can also explore the joint effects of recurrent sweeps and recent population size changes. These are not well understood, and are important for estimating the relative importance of background selection and recurrent sweeps in shaping genome-wide patterns of variability (e.g., Johri et al 2020).…”

Section: Applying Phase-type Theory To Other Population Genetic Modelmentioning

confidence: 99%

Studying models of balancing selection using phase-type theory

Zeng

Charlesworth

Hobolth

2020

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ABSTRACTBalancing selection is an important process, which maintains genetic variability in many functionally important genes. To increase our understanding of its effects on patterns of genetic diversity, we analyse two models of long-term balancing selection at a biallelic locus, one with a constant population size and the other with recent population size changes, as well as a model of recent balancing selection. We use time-inhomogeneous phase-type theory to obtain the expected properties of the gene tree at a neutral site linked to the target of selection, and the linkage disequilibrium (LD) between the selected and neutral sites. For long-term balancing selection, we show that selection targets with equilibrium allele frequencies close to 50% are easier to detect than targets with unequal allele frequencies. The target is also easier to identify after a population size reduction. The spread of a new mutation under balancing selection initially produces diversity patterns in linked neutral regions that are similar to those for a selective sweep caused by positive selection, including reduced diversity and an excess of both high and low frequency derived variants, as well as excess LD with the selected locus. Although the effects of recent balancing selection are more subtle, patterns of diversity and LD remain in a non-equilibrium state for a much longer period than with a sweep, and provide complementary information regarding the selection event. These results can be used for developing new methods for detecting loci under balancing selection, and illustrate the power of time-inhomogeneous phase-type theory, which can be applied to a wide range of population genetic problems.

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Toward an Evolutionarily Appropriate Null Model: Jointly Inferring Demography and Purifying Selection

Cited by 135 publications

References 97 publications

Power and limits of selection genome scans on temporal data from a selfing population

Power and limits of selection genome scans on temporal data from a selfing population

The impact of purifying and background selection on the inference of population history: problems and prospects

Studying models of balancing selection using phase-type theory

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