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S: PhyloBayes 3. A Bayesian software package for phylogenetic reconstruction and molecular dating
 Bioinformatics
"... Motivation: A variety of probabilistic models describing the evolution of DNA or protein sequences have been proposed for phylogenetic reconstruction or for molecular dating. However, there still lacks a common implementation allowing one to freely combine these independent features, so as to test t ..."
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Cited by 187 (8 self)
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Motivation: A variety of probabilistic models describing the evolution of DNA or protein sequences have been proposed for phylogenetic reconstruction or for molecular dating. However, there still lacks a common implementation allowing one to freely combine these independent features, so as to test their ability to jointly improve phylogenetic and dating accuracy. Results: We propose a software package, PhyloBayes 3, which can be used for conducting Bayesian phylogenetic reconstruction and molecular dating analyses, using a large variety of amino acid replacement and nucleotide substitution models, including empirical mixtures or nonparametric models, as well as alternative clock relaxation processes. Availability: PhyloBayes is freely available from our web site
Accounting for calibration uncertainty in phylogenetic estimation of evolutionary divergence times. Systematic Biology 58
, 2009
"... The estimation of phylogenetic divergence times from sequence data is an important component of many molecular evolutionary studies. There is now a general appreciation that the procedure of divergence dating is considerably more complex than that initially described in the 1960s by Zuckerkandl an ..."
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Cited by 90 (6 self)
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The estimation of phylogenetic divergence times from sequence data is an important component of many molecular evolutionary studies. There is now a general appreciation that the procedure of divergence dating is considerably more complex than that initially described in the 1960s by Zuckerkandl and Pauling (1962, 1965). In particular, there has been much critical attention toward the assumption of a global molecular clock, resulting in the development of increasingly sophisticated techniques for inferring divergence times from sequence data. In response to the documentation of widespread departures from clocklike behavior, a variety of local and relaxedclock methods have been proposed and implemented. Localclock methods permit different molecular clocks in different parts of the phy
The Impact of the Representation of Fossil Calibrations on Bayesian Estimation of Species Divergence Times
, 2009
"... Abstract.—Bayesian inference provides a powerful framework for integrating different sources of information (in particular, molecules and fossils) to derive estimates of species divergence times. Indeed, it is currently the only framework that can adequately account for uncertainties in fossil calib ..."
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Cited by 39 (13 self)
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Abstract.—Bayesian inference provides a powerful framework for integrating different sources of information (in particular, molecules and fossils) to derive estimates of species divergence times. Indeed, it is currently the only framework that can adequately account for uncertainties in fossil calibrations. We use 2 Bayesian Markov chain Monte Carlo programs, MULTIDIVTIME and MCMCTREE, to analyze 3 empirical data sets to estimate divergence times in amphibians, actinopterygians, and felids. We evaluate the impact of various factors, including the priors on rates and times, fossil calibrations, substitution model, the violation of the molecular clock and the ratedrift model, and the exact and approximate likelihood calculation. Assuming the molecular clock caused seriously biased time estimates when the clock is violated, but 2 different ratedrift models produced similar estimates. The prior on times, which incorporates fossilcalibration information, had the greatest impact on posterior time estimation. In particular, the strategies used by the 2 programs to incorporate minimum and maximumage bounds led to very different time priors and were responsible for large differences in posterior time estimates in a previous study. The results highlight the critical importance of fossil calibrations to molecular dating and the need for probabilistic modeling of fossil depositions, preservations, and sampling to provide statistical summaries of information
A phylogenetic model for investigating correlated evolution of substitution rates and continuous phenotypic characters
"... The comparative approach is routinely used to test for possible correlations between phenotypic or lifehistory traits. To correct for phylogenetic inertia, the method of independent contrasts assumes that continuous characters evolve along the phylogeny according to a multivariate Brownian process. ..."
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Cited by 24 (3 self)
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The comparative approach is routinely used to test for possible correlations between phenotypic or lifehistory traits. To correct for phylogenetic inertia, the method of independent contrasts assumes that continuous characters evolve along the phylogeny according to a multivariate Brownian process. Brownian diffusion processes have also been used to describe time variations of the parameters of the substitution process, such as the rate of substitution or the ratio of synonymous to nonsynonymous substitutions. Here, we develop a probabilistic framework for testing the coupling between continuous characters and parameters of the molecular substitution process. Rates of substitution and continuous characters are jointly modeled as a multivariate Brownian diffusion process of unknown covariance matrix. The covariancematrix, the divergence times and the phylogenetic variationsof substitution rates and continuous characters are all jointly estimated in a BayesianMonte Carlo framework, imposing on the covariance matrix a prior conjugate to the Brownian process so as to achieve a greater computational efficiency. The coupling between rates and phenotypes is assessed by measuring the posterior probability of positive or negative covariances, whereas divergence dates and phenotypic variations are marginally reconstructed in the context of the joint analysis. As an illustration, we apply the model to a set of 410 mammalian cytochrome b sequences. We observe a negative correlation between the rate of substitution and mass and longevity, which was previously observed. We also find a positive correlation between ω = dN/dS and mass and longevity, which we interpret as an indirect effect of variations of effective population size, thus in partial agreement with the nearly neutral theory. The method can easily be extended to any parameter of the substitution process and to any continuous phenotypic or environmental character.
Dating Primate Divergences through an Integrated Analysis of Palaeontological and Molecular Data
"... Abstract.—Estimation of divergence times is usually done using either the fossil record or sequence data from modern species. We provide an integrated analysis of palaeontological and molecular data to give estimates of primate divergence times that utilize both sources of information. The number of ..."
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Cited by 22 (4 self)
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Abstract.—Estimation of divergence times is usually done using either the fossil record or sequence data from modern species. We provide an integrated analysis of palaeontological and molecular data to give estimates of primate divergence times that utilize both sources of information. The number of preserved primate species discovered in the fossil record, along with their geological age distribution, is combined with the number of extant primate species to provide initial estimates of the primate and anthropoid divergence times. This is done by using a stochastic forwardsmodeling approach where speciation and fossil preservation and discovery are simulated forward in time. We use the posterior distribution from the fossil analysis as a prior distribution on node ages in a molecular analysis. Sequence data from two genomic
Molecular phylogenetics, principles and practice.
 Nature Reviews Genetics
, 2012
"... Systematics The inference of phylogenetic relationships among species and the use of such information to classify species. Taxonomy The description, classification and naming of species. Coalescent The process of joining ancestral lineages when the genealogical relationships of a random sample of s ..."
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Cited by 16 (0 self)
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Systematics The inference of phylogenetic relationships among species and the use of such information to classify species. Taxonomy The description, classification and naming of species. Coalescent The process of joining ancestral lineages when the genealogical relationships of a random sample of sequences from a modern population are traced back. Abstract  Phylogenies are important for addressing various biological questions such as relationships among species or genes, the origin and spread of viral infection and the demographic changes and migration patterns of species. The advancement of sequencing technologies has taken phylogenetic analysis to a new height. Phylogenies have permeated nearly every branch of biology, and the plethora of phylogenetic methods and software packages that are now available may seem daunting to an experimental biologist. Here, we review the major methods of phylogenetic analysis, including parsimony, distance, likelihood and Bayesian methods. We discuss their strengths and weaknesses and provide guidance for their use.
Approximate likelihood calculation on a phylogeny for Bayesian estimation of divergence times
 Mol Biol Evol
"... The molecular clock provides a powerful way to estimate species divergence times. If information on some species divergence times is available from the fossil or geological record, it can be used to calibrate a phylogeny and estimate divergence times for all nodes in the tree. The Bayesian method pr ..."
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Cited by 10 (3 self)
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The molecular clock provides a powerful way to estimate species divergence times. If information on some species divergence times is available from the fossil or geological record, it can be used to calibrate a phylogeny and estimate divergence times for all nodes in the tree. The Bayesian method provides a natural framework to incorporate different sources of information concerning divergence times, such as information in the fossil and molecular data. Current models of sequence evolution are intractable in a Bayesian setting, and Markov chain Monte Carlo (MCMC) is used to generate the posterior distribution of divergence times and evolutionary rates. This method is computationally expensive, as it involves the repeated calculation of the likelihood function. Here, we explore the use of Taylor expansion to approximate the likelihood during MCMC iteration. The approximation is much faster than conventional likelihood calculation. However, the approximation is expected to be poor when the proposed parameters are far from the likelihood peak. We explore the use of parameter transforms (square root, logarithm, and arcsine) to improve the approximation to the likelihood curve. We found that the new methods, particularly the arcsinebased transform, provided very good approximationsunder relaxed clock models and also under the global clock model when the global clock is not seriously violated. The approximation is poorer for analysis under the global clock when the global clock is seriously wrong and should thus not be used. The results suggest that the approximate method may be useful for Bayesian dating analysis using large data sets.
Phylogenetic Patterns of GCBiased Gene Conversion in Placental Mammals and the Evolutionary Dynamics of Recombination Landscapes
 Mol Biol Evol
, 2013
"... GCbiased gene conversion (gBGC) is a major evolutionary force shaping genomic nucleotide landscapes, distorting the estimation of the strength of selection, and having potentially deleterious effects on genomewide fitness. Yet, a global quantitative picture, at large evolutionary scale, of the re ..."
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Cited by 9 (1 self)
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GCbiased gene conversion (gBGC) is a major evolutionary force shaping genomic nucleotide landscapes, distorting the estimation of the strength of selection, and having potentially deleterious effects on genomewide fitness. Yet, a global quantitative picture, at large evolutionary scale, of the relative strength of gBGC compared with selection and random drift is still lacking. Furthermore, owing to its dependence on the local recombination rate, gBGC results in modulations of the substitution patterns along genomes and across time which, if correctly interpreted, may yield quantitative insights into the longterm evolutionary dynamics of recombination landscapes. Deriving a model of the substitution process at putatively neutral nucleotide positions from populationgenetics arguments, and accounting for amonglineage and amonggene effects, we propose a reconstruction of the variation in gBGC intensity at the scale of placental mammals, and of its scaling with bodysize and karyotypic traits. Our results are compatible with a simple population genetics model relating gBGC to effective population size and recombination rate. In addition, amonggene variation and phylogenetic patterns of exonspecific levels of gBGC reveal the presence of rugged recombination landscapes, and suggest that shortlived recombination hotspots are a general feature of placentals. Across placental mammals, variation in gBGC strength spans two orders of magnitude, at its lowest in apes, strongest in lagomorphs, microbats or tenrecs, and near or above the nearly neutral threshold in most other lineages. Combined with amonggene variation, such high levels of biased gene conversion are likely to significantly impact midly selected positions, and to represent a
A Hierarchical Bayesian Model for Calibrating Estimates of Species Divergence Times
 SYST. BIOL
, 2012
"... In Bayesian divergence time estimation methods, incorporating calibrating information from the fossil record is commonly done by assigning prior densities to ancestral nodes in the tree. Calibration prior densities are typically parametric distributions offset by minimum age estimates provided by t ..."
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Cited by 6 (4 self)
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In Bayesian divergence time estimation methods, incorporating calibrating information from the fossil record is commonly done by assigning prior densities to ancestral nodes in the tree. Calibration prior densities are typically parametric distributions offset by minimum age estimates provided by the fossil record. Specification of the parameters of calibration densities requires the user to quantify his or her prior knowledge of the age of the ancestral node relative to the age of its calibrating fossil. The values of these parameters can, potentially, result in biased estimates of node ages if they lead to overly informative prior distributions. Accordingly, determining parameter values that lead to adequate prior densities is not straightforward. In this study, I present a hierarchical Bayesian model for calibrating divergence time analyses with multiple fossil age constraints. This approach applies a Dirichlet process prior as a hyperprior on the parameters of calibration prior densities. Specifically, this model assumes that the rate parameters of exponential prior distributions on calibrated nodes are distributed according to a Dirichlet process, whereby the rate parameters are clustered into distinct parameter categories. Both simulated and biological data are analyzed to evaluate the performance of the Dirichlet process hyperprior. Compared with fixed exponential prior densities, the hierarchical Bayesian approach results in more accurate and precise estimates of internal node ages. When this hyperprior is applied using Markov chain Monte Carlo methods, the ages of calibrated nodes are sampled from mixtures of exponential distributions and uncertainty in the values of calibration density parameters is taken into account.