On the importance of skewed offspring distributions and background selection in virus population genetics

Irwin, Kristen K.; Laurent, Stefan; Matuszewski, Sebastian; Vuilleumier, Séverine; Ormond, Louise; Shim, Hyunjin; Bank, Claudia; Jensen, Jeffrey D.

doi:10.1038/hdy.2016.58

Cited by 52 publications

(49 citation statements)

References 88 publications

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“…This study marks the first multiple-merger coalescent with time-varying population sizes derived from a discrete time random mating model, and provides the first in-depth analyses of the joint inference of coalescent and demographic parameters. Since the Kingman coalescent represents a special case of the general class of multiple-merger coalescents (Irwin et al 2016;Spence et al 2016), it is interesting and encouraging to see that our analytical results -i.e., the time-change function (eq. 47) and the first expected coalescence times (eq.…”

Section: Discussionmentioning

confidence: 73%

Coalescent Processes with Skewed Offspring Distributions and non-Equilibrium Demography

Matuszewski

Hildebrandt

Jensen

2017

Preprint

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Non-equilibrium demography impacts coalescent genealogies leaving detectable, well-studied signatures of variation. However, similar genomic footprints are also expected under models of large reproductive skew, posing a serious problem when trying to make inference. Furthermore, current approaches consider only one of the two processes at a time, neglecting any genomic signal that could arise from their simultaneous effects, preventing the possibility of jointly inferring parameters relating to both offspring distribution and population history. Here, we develop an extended Moran model with exponential population growth, and demonstrate that the underlying ancestral process converges to a timeinhomogeneous psi-coalescent. However, by applying a non-linear change of time scaleanalogous to the Kingman coalescent -we find that the ancestral process can be rescaled to its time-homogeneous analogue, allowing the process to be simulated quickly and efficiently. Furthermore, we derive analytical expressions for the expected site-frequency spectrum under the time-inhomogeneous psi-coalescent and develop an approximate-likelihood framework for the joint estimation of the coalescent and growth parameters. By means of extensive simulation, we demonstrate that both can be estimated accurately given linkage equilibrium, while linkage disequilibrium systematically biases growth rate estimates. In addition, not accounting for demography can lead to serious biases in the inferred coalescent model, with broad implications for genomic studies ranging from ecology to conservation biology. Finally, we use our method to analyze sequence data from Japanese sardine populations and find evidence of high variation in individual reproductive success, but few signs of a recent demographic expansion.

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Section: Discussionmentioning

confidence: 73%

Coalescent Processes with Skewed Offspring Distributions and non-Equilibrium Demography

Matuszewski

Hildebrandt

Jensen

2017

Preprint

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“…However, aspects of viral biology render the application of standard population genetic inference methods problematic. Namely, existing methodologies for analyzing time-sampled polymorphism data are generally developed around the Kingman coalescent framework and the Wright-Fisher (WF) model (Wright 1931;Kingman 1982) and are of questionable applicability to organisms typified by large variances in offspring distributions, or so-called "sweepstakes reproduction," including not only viruses but many classes of prokaryotes, fungi, plants, and animals (reviewed in Tellier and Lemaire 2014;Irwin et al 2016).…”

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confidence: 99%

Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions

Sackman

Harris²,

Jensen³

2019

Genetics

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The recent increase in time-series population genomic data from experimental, natural, and ancient populations has been accompanied by a promising growth in methodologies for inferring demographic and selective parameters from such data. However, these methods have largely presumed that the populations of interest are well-described by the Kingman coalescent. In reality, many groups of organisms, including viruses, marine organisms, and some plants, protists, and fungi, typified by high variance in progeny number, may be best characterized by multiple-merger coalescent models. Estimation of population genetic parameters under Wright-Fisher assumptions for these organisms may thus be prone to serious mis-inference. We propose a novel method for the joint inference of demography and selection under the C-coalescent model, termed Multiple-Merger Coalescent Approximate Bayesian Computation, or MMC-ABC. We first demonstrate mis-inference under the Kingman, and then exhibit the superior performance of MMC-ABC under conditions of skewed offspring distributions. In order to highlight the utility of this approach, we reanalyzed previously published drug-selection lines of influenza A virus. We jointly inferred the extent of progeny-skew inherent to viral replication and identified putative drug-resistance mutations.

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“…Taking these points into account, a more general class of models, so-called multiple-merger coalescent (MMC) models, have been developed (e.g., Bolthausen and Sznitman 1998;Pitman 1999;Sagitov 1999;Schweinsberg 2000;Möhle and Sagitov 2001; reviewed in Tellier and Lemaire 2014), aiming to generalize the Kingman coalescent model (Wakeley 2013). As for the latter, these MMC models can often be derived from Moran models, generalized to allow multiple offspring per individual (Eldon and Wakeley 2006;Huillet and Möhle 2013; see also review of Irwin et al 2016).…”

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confidence: 99%

Coalescent Processes with Skewed Offspring Distributions and Nonequilibrium Demography

et al. 2018

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Nonequilibrium demography impacts coalescent genealogies leaving detectable, well-studied signatures of variation. However, similar genomic footprints are also expected under models of large reproductive skew, posing a serious problem when trying to make inference. Furthermore, current approaches consider only one of the two processes at a time, neglecting any genomic signal that could arise from their simultaneous effects, preventing the possibility of jointly inferring parameters relating to both offspring distribution and population history. Here, we develop an extended Moran model with exponential population growth, and demonstrate that the underlying ancestral process converges to a time-inhomogeneous psi-coalescent. However, by applying a nonlinear change of time scale-analogous to the Kingman coalescent-we find that the ancestral process can be rescaled to its time-homogeneous analog, allowing the process to be simulated quickly and efficiently. Furthermore, we derive analytical expressions for the expected site-frequency spectrum under the time-inhomogeneous psi-coalescent, and develop an approximate-likelihood framework for the joint estimation of the coalescent and growth parameters. By means of extensive simulation, we demonstrate that both can be estimated accurately from whole-genome data. In addition, not accounting for demography can lead to serious biases in the inferred coalescent model, with broad implications for genomic studies ranging from ecology to conservation biology. Finally, we use our method to analyze sequence data from Japanese sardine populations, and find evidence of high variation in individual reproductive success, but few signs of a recent demographic expansion.

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On the importance of skewed offspring distributions and background selection in virus population genetics

Cited by 52 publications

References 88 publications

Coalescent Processes with Skewed Offspring Distributions and non-Equilibrium Demography

Coalescent Processes with Skewed Offspring Distributions and non-Equilibrium Demography

Inferring Demography and Selection in Organisms Characterized by Skewed Offspring Distributions

Coalescent Processes with Skewed Offspring Distributions and Nonequilibrium Demography

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