The Implications of Lineage-Specific Rates for Divergence Time Estimation

Abstract Rate variation adds considerable complexity to divergence time estimation in molecular phylogenies. Here, we evaluate the impact of lineage-specific rates—which we define as among-branch-rate-variation that acts consistently across the entire genome. We compare its impact to residual rates—defined as among-branch-rate-variation that shows a different pattern of rate variation at each sampled locus, and gene-specific rates—defined as variation in the average rate across all branches at each sampled locus. We show that lineage-specific rates lead to erroneous divergence time estimates, regardless of how many loci are sampled. Further, we show that stronger lineage-specific rates lead to increasing error. This contrasts to residual rates and gene-specific rates, where sampling more loci significantly reduces error. If divergence times are inferred in a Bayesian framework, we highlight that error caused by lineage-specific rates significantly reduces the probability that the 95% highest posterior density includes the correct value, and leads to sensitivity to the prior. Use of a more complex rate prior—which has recently been proposed to model rate variation more accurately—does not affect these conclusions. Finally, we show that the scale of lineage-specific rates used in our simulation experiments is comparable to that of an empirical data set for the angiosperm genus Ipomoea. Taken together, our findings demonstrate that lineage-specific rates cause error in divergence time estimates, and that this error is not overcome by analyzing genomic scale multilocus data sets. [Divergence time estimation; error; rate variation.]

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Uncertainty in divergence time estimation

Systematic Biology ◽

10.1093/sysbio/syaa096 ◽

2020 ◽

Author(s):

Tom Carruthers ◽

Robert W Scotland

Keyword(s):

Fossil Record ◽

Academic Research ◽

Divergence Time ◽

Time Estimation ◽

Divergence Time Estimation ◽

Diversification Rates ◽

Divergence Time Estimates ◽

Use Of Time ◽

Time Estimates ◽

Highly Sensitive

Abstract Understanding and representing uncertainty is crucial in academic research, because it enables studies to build on the conclusions of previous studies, leading to robust advances in a particular field. Here, we evaluate the nature of uncertainty and the manner by which it is represented in divergence time estimation, a field that is fundamental to many aspects of macroevolutionary research, and where there is evidence that uncertainty has been seriously underestimated. We address this issue in the context of methods used in divergence time estimation, and with respect to the manner by which time-calibrated phylogenies are interpreted. With respect to methods, we discuss how the assumptions underlying different methods may not adequately reflect uncertainty about molecular evolution, the fossil record, or diversification rates. Therefore, divergence time estimates may not adequately reflect uncertainty, and may be directly contradicted by subsequent findings. For the interpretation of time-calibrated phylogenies, we discuss how the use of time-calibrated phylogenies for reconstructing general evolutionary timescales leads to inferences about macroevolution that are highly sensitive to methodological limitations in how uncertainty is accounted for. By contrast, we discuss how the use of time-calibrated phylogenies to test specific hypotheses leads to inferences about macroevolution that are less sensitive to methodological limitations. Given that many biologists wish to use time-calibrated phylogenies to reconstruct general evolutionary timescales, we conclude that the development of methods of divergence time estimation that adequately account for uncertainty is necessary.

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Using Phylogenomic Data to Explore the Effects of Relaxed Clocks and Calibration Strategies on Divergence Time Estimation: Primates as a Test Case

10.1101/201327 ◽

2017 ◽

Cited By ~ 1

Author(s):

Mario dos Reis ◽

Gregg F. Gunnell ◽

José Barba-Montoya ◽

Alex Wilkins ◽

Ziheng Yang ◽

...

Keyword(s):

Sequence Data ◽

Divergence Time ◽

Time Estimation ◽

Test Case ◽

Base Pairs ◽

Molecular Sequence Data ◽

Divergence Time Estimation ◽

Divergence Time Estimates ◽

Time Estimates ◽

Clock Models

AbstractPrimates have long been a test case for the development of phylogenetic methods for divergence time estimation. Despite a large number of studies, however, the timing of origination of crown Primates relative to the K-Pg boundary and the timing of diversification of the main crown groups remain controversial. Here we analysed a dataset of 372 taxa (367 Primates and 5 outgroups, 61 thousand base pairs) that includes nine complete primate genomes (3.4 million base pairs). We systematically explore the effect of different interpretations of fossil calibrations and molecular clock models on primate divergence time estimates. We find that even small differences in the construction of fossil calibrations can have a noticeable impact on estimated divergence times, especially for the oldest nodes in the tree. Notably, choice of molecular rate model (auto-correlated or independently distributed rates) has an especially strong effect on estimated times, with the independent rates model producing considerably more ancient estimates for the deeper nodes in the phylogeny. We implement thermodynamic integration, combined with Gaussian quadrature, in the program MCMCTree, and use it to calculate Bayes factors for clock models. Bayesian model selection indicates that the auto-correlated rates model fits the primate data substantially better, and we conclude that time estimates under this model should be preferred. We show that for eight core nodes in the phylogeny, uncertainty in time estimates is close to the theoretical limit imposed by fossil uncertainties. Thus, these estimates are unlikely to be improved by collecting additional molecular sequence data. All analyses place the origin of Primates close to the K-Pg boundary, either in the Cretaceous or straddling the boundary into the Palaeogene.

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Ignoring stratigraphic age uncertainty leads to erroneous estimates of species divergence times under the fossilized birth-death process

10.1101/477133 ◽

2018 ◽

Cited By ~ 1

Author(s):

Joëlle Barido-Sottani ◽

Gabriel Aguirre-Fernández ◽

Melanie Hopkins ◽

Tanja Stadler ◽

Rachel Warnock

Keyword(s):

Divergence Time ◽

Time Estimation ◽

Death Process ◽

Divergence Times ◽

Point Estimate ◽

Species Divergence ◽

Divergence Time Estimation ◽

Divergence Time Estimates ◽

Time Estimates ◽

Birth Death

AbstractFossil information is essential for estimating species divergence times, and can be integrated into Bayesian phylogenetic inference using the fossilized birth-death (FBD) process. An important aspect of palaeontological data is the uncertainty surrounding specimen ages, which can be handled in different ways during inference. The most common approach is to fix fossil ages to a point estimate within the known age interval. Alternatively, age uncertainty can be incorporated by using priors, and fossil ages are then directly sampled as part of the inference. This study presents a comparison of alternative approaches for handling fossil age uncertainty in analysis using the FBD process. Based on simulations, we find that fixing fossil ages to the midpoint or a random point drawn from within the stratigraphic age range leads to biases in divergence time estimates, while sampling fossil ages leads to estimates that are similar to inferences that employ the correct ages of fossils. Second, we show a comparison using an empirical dataset of extant and fossil cetaceans, which confirms that different methods of handling fossil age uncertainty lead to large differences in estimated node ages. Stratigraphic age uncertainty should thus not be ignored in divergence time estimation and instead should be incorporated explicitly.

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Ignoring stratigraphic age uncertainty leads to erroneous estimates of species divergence times under the fossilized birth–death process

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2019.0685 ◽

2019 ◽

Vol 286 (1902) ◽

pp. 20190685 ◽

Cited By ~ 14

Author(s):

Joëlle Barido-Sottani ◽

Gabriel Aguirre-Fernández ◽

Melanie J. Hopkins ◽

Tanja Stadler ◽

Rachel Warnock

Keyword(s):

Divergence Time ◽

Time Estimation ◽

Death Process ◽

Divergence Times ◽

Point Estimate ◽

Species Divergence ◽

Divergence Time Estimation ◽

Divergence Time Estimates ◽

Time Estimates ◽

Birth Death

Fossil information is essential for estimating species divergence times, and can be integrated into Bayesian phylogenetic inference using the fossilized birth–death (FBD) process. An important aspect of palaeontological data is the uncertainty surrounding specimen ages, which can be handled in different ways during inference. The most common approach is to fix fossil ages to a point estimate within the known age interval. Alternatively, age uncertainty can be incorporated by using priors, and fossil ages are then directly sampled as part of the inference. This study presents a comparison of alternative approaches for handling fossil age uncertainty in analysis using the FBD process. Based on simulations, we find that fixing fossil ages to the midpoint or a random point drawn from within the stratigraphic age range leads to biases in divergence time estimates, while sampling fossil ages leads to estimates that are similar to inferences that employ the correct ages of fossils. Second, we show a comparison using an empirical dataset of extant and fossil cetaceans, which confirms that different methods of handling fossil age uncertainty lead to large differences in estimated node ages. Stratigraphic age uncertainty should thus not be ignored in divergence time estimation and instead should be incorporated explicitly.

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Assessing the quality of molecular divergence time estimates by fossil calibrations and fossil–based model selection

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2004.1523 ◽

2004 ◽

Vol 359 (1450) ◽

pp. 1477-1483 ◽

Cited By ~ 126

Author(s):

Thomas J. Near ◽

Michael J. Sanderson

Keyword(s):

Cross Validation ◽

Sequence Data ◽

Divergence Time ◽

Evolutionary Model ◽

Time Estimation ◽

Optimal Estimation ◽

Divergence Time Estimation ◽

Fossil Calibration ◽

Divergence Time Estimates ◽

The Impact

Estimates of species divergence times using DNA sequence data are playing an increasingly important role in studies of evolution, ecology and biogeography. Most work has centred on obtaining appropriate kinds of data and developing optimal estimation procedures, whereas somewhat less attention has focused on the calibration of divergences using fossils. Case studies with multiple fossil calibration points provide important opportunities to examine the divergence time estimation problem in new ways. We discuss two cross–validation procedures that address different aspects of inference in divergence time estimation. ‘Fossil cross–validation’ is a procedure used to identify the impact of different individual calibrations on overall estimation. This can identify fossils that have an exceptionally large error effect and may warrant further scrutiny. ‘Fossil–based model cross–validation’ is an entirely different procedure that uses fossils to identify the optimal model of molecular evolution in the context of rate smoothing or other inference methods. Both procedures were applied to two recent studies: an analysis of monocot angiosperms with eight fossil calibrations and an analysis of placental mammals with nine fossil calibrations. In each case, fossil calibrations could be ranked from most to least influential, and in one of the two studies, the fossils provided decisive evidence about the optimal molecular evolutionary model.

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The Past Sure Is Tense: On Interpreting Phylogenetic Divergence Time Estimates

10.1101/113720 ◽

2017 ◽

Cited By ~ 2

Author(s):

Joseph W. Brown ◽

Stephen A. Smith

Keyword(s):

Bayesian Analysis ◽

Early Cretaceous ◽

Fossil Record ◽

Divergence Time ◽

Time Estimation ◽

Inference Problem ◽

Divergence Time Estimation ◽

Divergence Time Estimates ◽

The Impact ◽

Pseudo Data

AbstractDivergence time estimation — the calibration of a phylogeny to geological time — is an integral first step in modelling the tempo of biological evolution (traits and lineages). However, despite increasingly sophisticated methods to infer divergence times from molecular genetic sequences, the estimated age of many nodes across the tree of life contrast significantly and consistently with timeframes conveyed by the fossil record. This is perhaps best exemplified by crown angiosperms, where molecular clock (Triassic) estimates predate the oldest (Early Cretaceous) undisputed angiosperm fossils by tens of millions of years or more. While the incompleteness of the fossil record is a common concern, issues of data limitation and model inadequacy are viable (if underexplored) alternative explanations. In this vein, Beaulieu et al. (2015) convincingly demonstrated how methods of divergence time inference can be misled by both (i) extreme state-dependent molecular substitution rate heterogeneity and (ii) biased sampling of representative major lineages. These results demonstrate the impact of (potentially common) model violations. Here, we suggest another potential challenge: that the configuration of the statistical inference problem (i.e., the parameters, their relationships, and associated priors) alone may preclude the reconstruction of the paleontological timeframe for the crown age of angiosperms. We demonstrate, through sampling from the joint prior (formed by combining the tree (diversification) prior with the calibration densities specified for fossil-calibrated nodes) that with no data present at all, that, an Early Cretaceous crown angiosperms is rejected (i.e., has essentially zero probability). More worrisome, however, is that, for the 24 nodes calibrated by fossils, almost all have indistinguishable marginal prior and posterior age distributions when employing routine lognormal fossil calibration priors. These results indicate that there is inadequate information in the data to overrule the joint prior. Given that these calibrated nodes are strategically placed in disparate regions of the tree, they act to anchor the tree scaffold, and so the posterior inference for the tree as a whole is largely determined by the pseudo-data present in the (often arbitrary) calibration densities. We recommend, as for any Bayesian analysis, that marginal prior and posterior distributions be carefully compared to determine whether signal is coming from the data or prior belief, especially for parameters of direct interest. This recommendation is not novel. However, given how rarely such checks are carried out in evolutionary biology, it bears repeating. Our results demonstrate the fundamental importance of prior/posterior comparisons in any Bayesian analysis, and we hope that they further encourage both researchers and journals to consistently adopt, this crucial step as standard practice. Finally, we note that the results presented here do not refute the biological modelling concerns identified by Beaulieu et al. (2015). Both sets of issues remain apposite to the goals of accurate divergence time estimation, and only by considering them in tandem can we move forward more confidently. [marginal priors; information content; diptych; divergence time estimation; fossil record; BEAST; angiosperms.]

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Using a GTR+Γ substitution model for dating sequence divergence when stationarity and time-reversibility assumptions are violated

Bioinformatics ◽

10.1093/bioinformatics/btaa820 ◽

2020 ◽

Vol 36 (Supplement_2) ◽

pp. i884-i894

Author(s):

Jose Barba-Montoya ◽

Qiqing Tao ◽

Sudhir Kumar

Keyword(s):

Divergence Time ◽

Sequence Divergence ◽

Molecular Dating ◽

Divergence Times ◽

Time Reversibility ◽

Sequence Alignments ◽

Divergence Time Estimates ◽

Time Estimates ◽

Substitution Process ◽

The Impact

Abstract Motivation As the number and diversity of species and genes grow in contemporary datasets, two common assumptions made in all molecular dating methods, namely the time-reversibility and stationarity of the substitution process, become untenable. No software tools for molecular dating allow researchers to relax these two assumptions in their data analyses. Frequently the same General Time Reversible (GTR) model across lineages along with a gamma (+Γ) distributed rates across sites is used in relaxed clock analyses, which assumes time-reversibility and stationarity of the substitution process. Many reports have quantified the impact of violations of these underlying assumptions on molecular phylogeny, but none have systematically analyzed their impact on divergence time estimates. Results We quantified the bias on time estimates that resulted from using the GTR + Γ model for the analysis of computer-simulated nucleotide sequence alignments that were evolved with non-stationary (NS) and non-reversible (NR) substitution models. We tested Bayesian and RelTime approaches that do not require a molecular clock for estimating divergence times. Divergence times obtained using a GTR + Γ model differed only slightly (∼3% on average) from the expected times for NR datasets, but the difference was larger for NS datasets (∼10% on average). The use of only a few calibrations reduced these biases considerably (∼5%). Confidence and credibility intervals from GTR + Γ analysis usually contained correct times. Therefore, the bias introduced by the use of the GTR + Γ model to analyze datasets, in which the time-reversibility and stationarity assumptions are violated, is likely not large and can be reduced by applying multiple calibrations. Availability and implementation All datasets are deposited in Figshare: https://doi.org/10.6084/m9.figshare.12594638.

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Reliable confidence intervals for RelTime estimates of evolutionary divergence times

10.1101/677286 ◽

2019 ◽

Cited By ~ 1

Author(s):

Qiqing Tao ◽

Koichiro Tamura ◽

Beatriz Mello ◽

Sudhir Kumar

Keyword(s):

Confidence Intervals ◽

Divergence Time ◽

Simulated Data ◽

Molecular Dating ◽

Divergence Times ◽

Rate Variation ◽

Evolutionary Divergence ◽

Posterior Density ◽

Divergence Time Estimates ◽

Highest Posterior Density

AbstractConfidence intervals (CIs) depict the statistical uncertainty surrounding evolutionary divergence time estimates. They capture variance contributed by the finite number of sequences and sites used in the alignment, deviations of evolutionary rates from a strict molecular clock in a phylogeny, and uncertainty associated with clock calibrations. Reliable tests of biological hypotheses demand reliable CIs. However, current non-Bayesian methods may produce unreliable CIs because they do not incorporate rate variation among lineages and interactions among clock calibrations properly. Here, we present a new analytical method to calculate CIs of divergence times estimated using the RelTime method, along with an approach to utilize multiple calibration uncertainty densities in these analyses. Empirical data analyses showed that the new methods produce CIs that overlap with Bayesian highest posterior density (HPD) intervals. In the analysis of computer-simulated data, we found that RelTime CIs show excellent average coverage probabilities, i.e., the true time is contained within the CIs with a 95% probability. These developments will encourage broader use of computationally-efficient RelTime approach in molecular dating analyses and biological hypothesis testing.

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