The bounded coalescent model: conditioning a genealogy on a minimum root date

The coalescent model represents how individuals sampled from a population may have originated from a last common ancestor. The bounded coalescent model is obtained by conditioning the coalescent model such that the last common ancestor must have existed after a certain date. This conditioned model arises in a variety of applications, such as speciation, horizontal gene transfer or transmission analysis, and yet the bounded coalescent model has not been previously analysed in detail. Here we describe a new algorithm to simulate from this model directly, without resorting to rejection sampling. We show that this direct simulation algorithm is more computationally efficient than the rejection sampling approach. We also show how to calculate the probability of the last common ancestor occurring after a given date, which is required to compute the probability of realisations under the bounded coalescent model. Our results are applicable in both the isochronous (when all samples have the same date) and heterochronous (where samples can have different dates) settings. We explore the effect of setting a bound on the date of the last common ancestor, and show that it affects a number of properties of the resulting phylogenies. All our methods are implemented in a new R package called BoundedCoalescent which is freely available online.

On the inference of complex phylogenetic networks by Markov Chain Monte-Carlo

For various species, high quality sequences and complete genomes are nowadays available for many individuals. This makes data analysis challenging, as methods need not only to be accurate, but also time efficient given the tremendous amount of data to process. In this article, we introduce an efficient method to infer the evolutionary history of individuals under the multispecies coalescent model in networks (MSNC). Phylogenetic networks are an extension of phylogenetic trees that can contain reticulate nodes, which allow to model complex biological events such as horizontal gene transfer, hybridization and introgression. We present a novel way to compute the likelihood of biallelic markers sampled along genomes whose evolution involved such events. This likelihood computation is at the heart of a Bayesian network inference method called SnappNet, as it extends the Snapp method inferring evolutionary trees under the multispecies coalescent model, to networks. SnappNet is available as a package of the well-known beast 2 software. Recently, the MCMC_BiMarkers method, implemented in PhyloNet, also extended Snapp to networks. Both methods take biallelic markers as input, rely on the same model of evolution and sample networks in a Bayesian framework, though using different methods for computing priors. However, SnappNet relies on algorithms that are exponentially more time-efficient on non-trivial networks. Using simulations, we compare performances of SnappNet and MCMC_BiMarkers. We show that both methods enjoy similar abilities to recover simple networks, but SnappNet is more accurate than MCMC_BiMarkers on more complex network scenarios. Also, on complex networks, SnappNet is found to be extremely faster than MCMC_BiMarkers in terms of time required for the likelihood computation. We finally illustrate SnappNet performances on a rice data set. SnappNet infers a scenario that is consistent with previous results and provides additional understanding of rice evolution.

Multiple Loci Selection with Multi-Way Epistasis in Coalescence with Recombination

As studies move into deeper characterization of the impact of selection through non-neutral mutations in whole genome population genetics, modeling for selection becomes crucial. Moreover, epistasis has long been recognized as a significant component in understanding the evolution of complex genetic systems. We present a backward coalescent model, EpiSimRA, that accommodates multiple loci selection, with multi-way (k-way) epistasis for any arbitrary k. Starting from arbitrary extant populations with epistatic sites, we trace the Ancestral Recombination Graph (ARG), sampling relevant recombination and coalescent events. Our framework allows for studying different complex evolutionary scenarios in the presence of selective sweeps, positive and negative selection with multiway epistasis. We also present a forward counterpart of the coalescent model based on a Wright-Fisher (WF) process, which we use as a validation framework, comparing the hallmarks of the ARG between the two. We provide the first framework that allows a nose-to-nose comparison of multiway epistasis in a coalescent simulator with its forward counterpart with respect to the hallmarks of the ARG. We demonstrate, through extensive experiments, that EpiSimRA is consistently superior in terms of performance (seconds vs. hours) in comparison to the forward model without compromising on its accuracy.

Multiple Loci Selection with Multi-way Epistasis in Coalescence with Recombination

As studies move into deeper characterization of the impact of selection through non-neutral mutations in whole genome population genetics, modeling for selection becomes crucial. Moreover, epistasis has long been recognized as a significant component in understanding evolution of complex genetic systems. We present a backward coalescent model EpiSimRA, that builds multiple loci selection, with multiway (k-way) epistasis for any arbitrary k. Starting from arbitrary extant populations with epistatic sites, we trace the Ancestral Recombination Graph (ARG), sampling relevant recombination and coalescent events. Our framework allows for studying different complex evolutionary scenarios in the presence of selective sweeps, positive and negative selection with multiway epistasis. We also present a forward counterpart of the coalescent model based on a Wright-Fisher (WF) process which we use as a validation framework, comparing the hallmarks of the ARG between the two. We provide the first framework that allows a nose-to-nose comparison of multiway epistasis in a coalescent simulator with its forward counterpart with respect to the hallmarks of the ARG. We demonstrate through extensive experiments, that EpiSimRA is consistently superior in term of performance (seconds vs. hours) in comparison to the forward model without compromising on its accuracy.

Gene Tree Discord, Simplex Plots, and Statistical Tests under the Coalescent

A simple graphical device, the simplex plot of quartet concordance factors, is introduced to aid in the exploration of a collection of gene trees on a common set of taxa. A single plot summarizes all gene tree discord and allows for visual comparison to the expected discord from the multispecies coalescent model (MSC) of incomplete lineage sorting on a species tree. A formal statistical procedure is described that can quantify the deviation from expectation for each subset of four taxa, suggesting when the data are not in accord with the MSC, and thus that either gene tree inference error is substantial or a more complex model such as that on a network may be required. If the collection of gene trees is in accord with the MSC, the plots reveal when substantial incomplete lineage sorting is present. Applications to both simulated and empirical multilocus data sets illustrate the insights provided. [Gene tree discordance; hypothesis test; multispecies coalescent model; quartet concordance factor; simplex plot; species tree].

Identifiability of speciation times under the multispecies coalescent

The advent of rapid and inexpensive sequencing technologies has necessitated the development of computationally efficient methods for analyzing sequence data for many genes simultaneously in a phylogenetic framework. The coalescent process is the most commonly used model for linking the underlying genealogies of individual genes with the global species-level phylogeny, but inference under the coalescent model is computationally daunting in the typical inference frameworks (e.g., the likelihood and Bayesian frameworks) due to the dimensionality of the space of both gene trees and species trees. Here we consider estimation of the branch lengths in a fixed species tree, and show that these branch lengths are identifiable. We also show that in the case of four taxa simple estimators for the branch lengths can be derived based on observed site pattern frequencies. Properties of these estimators, such as their asymptotic variances and large-sample distributions, are examined, and performance of the estimators is assessed using simulation. Finally, we use these estimators to develop a hypothesis test that can be limit species under the coalescent model.

MSCquartets 1.0: Quartet methods for species trees and networks under the multispecies coalescent model in R

Summary MSCquartets is an R package for species tree hypothesis testing, inference of species trees, and inference of species networks under the Multispecies Coalescent model of incomplete lineage sorting and its network analog. Input for these analyses are collections of metric or topological locus trees which are then summarized by the quartets displayed on them. Results of hypothesis tests at user-supplied levels are displayed in a simplex plot by color-coded points. The package implements the QDC and WQDC algorithms for topological and metric species tree inference, and the NANUQ algorithm for level-1 topological species network inference, all of which give statistically consistent estimators under the model. Availability MSCquartets is available through the Comprehensive R Archive Network: https://CRAN.R-project.org/package=MSCquartets. Supplementary information Supplementary materials, including example data and analyses, are incorporated into the package.

On the inference of complex phylogenetic networks by Markov Chain Monte-Carlo

For various species, high quality sequences and complete genomes are nowadays available for many individuals. This makes data analysis challenging, as methods need not only to be accurate, but also time efficient given the tremendous amount of data to process. In this article, we introduce an efficient method to infer the evolutionary history of individuals under the multispecies coalescent model in networks (MSNC). Phylogenetic networks are an extension of phylogenetic trees that can contain reticulate nodes, which allow to model complex biological events such as horizontal gene transfer, hybridization, introgression and recombination. We present a novel way to compute the likelihood of biallelic markers sampled along genomes whose evolution involved such events. This likelihood computation is at the heart of a Bayesian network inference method called SnappNet, as it extends the Snapp method [1] inferring evolutionary trees under the multispecies coalescent model, to networks. SnappNet is available as a package of the well-known beast 2 software.Recently, the MCMCBiMarkers method [2] also extended Snapp to networks. Both methods take biallelic markers as input, rely on the same model of evolution and sample networks in a Bayesian framework, though using different methods for computing priors. However, SnappNet relies on algorithms that are exponentially more time-efficient on non-trivial networks. Using extensive simulations, we compare performances of SnappNet and MCMCBiMarkers. We show that both methods enjoy similar abilities to recover simple networks, but SnappNet is more accurate than MCMCBiMarkers on more complex network scenarios. Also, on complex networks, SnappNet is found to be extremely faster than MCMCBiMarkers in terms of time required for the likelihood computation. We finally illustrate SnappNet performances on a rice data set. SnappNet infers a scenario that is compatible with simpler schemes proposed so far and provides additional understanding of rice evolution.Author summaryNowadays, to make the best use of the vast amount of genomic data at our disposal, there is a real need for methods able to model complex biological mechanisms such as hybridization and introgression. Understanding such mechanisms can help geneticists to elaborate strategies in crop improvement that may help reducing poverty and dealing with climate change. However, reconstructing such evolution scenarios is challenging. Indeed, the inference of phylogenetic networks, which explicitly model reticulation events such as hybridization and introgression, requires high computational resources. Then, on large data sets, biologists generally deduce reticulation events indirectly using species tree inference tools.In this context, we present a new Bayesian method, called SnappNet, dedicated to phylogenetic network inference. Our method is competitive in terms of execution speed with respect to its competitors. This speed gain enables us to consider more complex evolution scenarios during Bayesian analyses. When applied to rice genomic data, SnappNet suggested a new evolution scenario, compatible with the existing ones: it posits cAus as the result of an early combination between the Indica and Japonica lineages, followed by a later combination between the cAus and Japonica lineages to derive cBasmati. This accounts for the well-documented wide hybrid compatibility of cAus.

A Simulation Study to Examine the Information Content in Phylogenomic Data Sets under the Multispecies Coalescent Model

We use computer simulation to examine the information content in multilocus data sets for inference under the multispecies coalescent model. Inference problems considered include estimation of evolutionary parameters (such as species divergence times, population sizes, and cross-species introgression probabilities), species tree estimation, and species delimitation based on Bayesian comparison of delimitation models. We found that the number of loci is the most influential factor for almost all inference problems examined. Although the number of sequences per species does not appear to be important to species tree estimation, it is very influential to species delimitation. Increasing the number of sites and the per-site mutation rate both increase the mutation rate for the whole locus and these have the same effect on estimation of parameters, but the sequence length has a greater effect than the per-site mutation rate for species tree estimation. We discuss the computational costs when the data size increases and provide guidelines concerning the subsampling of genomic data to enable the application of full-likelihood methods of inference.