scholarly journals Exploring uncertainty in the calibration of the molecular clock

2011 ◽  
Vol 8 (1) ◽  
pp. 156-159 ◽  
Author(s):  
Rachel C. M. Warnock ◽  
Ziheng Yang ◽  
Philip C. J. Donoghue

Calibration is a critical step in every molecular clock analysis but it has been the least considered. Bayesian approaches to divergence time estimation make it possible to incorporate the uncertainty in the degree to which fossil evidence approximates the true time of divergence. We explored the impact of different approaches in expressing this relationship, using arthropod phylogeny as an example for which we established novel calibrations. We demonstrate that the parameters distinguishing calibration densities have a major impact upon the prior and posterior of the divergence times, and it is critically important that users evaluate the joint prior distribution of divergence times used by their dating programmes. We illustrate a procedure for deriving calibration densities in Bayesian divergence dating through the use of soft maximum constraints.

2020 ◽  
Vol 12 (7) ◽  
pp. 1087-1098
Author(s):  
Alan J S Beavan ◽  
Philip C J Donoghue ◽  
Mark A Beaumont ◽  
Davide Pisani

Abstract Relaxed molecular clock methods allow the use of genomic data to estimate divergence times across the tree of life. This is most commonly achieved in Bayesian analyses where the molecular clock is calibrated a priori through the integration of fossil information. Alternatively, fossil calibrations can be used a posteriori, to transform previously estimated relative divergence times that were inferred without considering fossil information, into absolute divergence times. However, as branch length is the product of the rate of evolution and the duration in time of the considered branch, the extent to which a posteriori calibrated, relative divergence time methods can disambiguate time and rate, is unclear. Here, we use forward evolutionary simulations and compare a priori and a posteriori calibration strategies using different molecular clock methods and models. Specifically, we compare three Bayesian methods, the strict clock, uncorrelated clock and autocorrelated clock, and the non-Bayesian algorithm implemented in RelTime. We simulate phylogenies with multiple, independent substitution rate changes and show that correct timescales cannot be inferred without the use of calibrations. Under our simulation conditions, a posteriori calibration strategies almost invariably inferred incorrect rate changes and divergence times. The a priori integration of fossil calibrations is fundamental in these cases to improve the accuracy of the estimated divergence times. Relative divergence times and absolute timescales derived by calibrating relative timescales to geological time a posteriori appear to be less reliable than a priori calibrated, timescales.


2020 ◽  
Author(s):  
Rachel Warnock ◽  
Jan Engelstädter

The molecular clock in combination with evidence from the geological record can be applied to infer the timing and dynamics of evolutionary events. This has enormous potential to shed light on the complex and often evasive evolution of parasites. Here, we provide an overview of molecular clock methodology and recent advances that increase the potential for the study of host-parasite coevolutionary dynamics, with a focus on Bayesian approaches to divergence time estimation. We highlight the challenges in applying these methods to the study of parasites, including the nature of parasite genomes, the incompleteness of the rock and fossil records, and the complexity of host-parasite interactions. Developments in models of molecular evolution and approaches to deriving temporal constraints from geological evidence will help overcome some of these issues. However, we also describe a case study in which the timescale of host-parasite coevolution cannot easily be inferred using existing methods – that of the alpha-proteobacteria Wolbachia. We conclude by providing a prospective on future methodological developments and data collection that will facilitate in understanding the role of parasitism in deep time.


2016 ◽  
Vol 12 (11) ◽  
pp. 20160609 ◽  
Author(s):  
G. T. Lloyd ◽  
D. W. Bapst ◽  
M. Friedman ◽  
K. E. Davis

Branch lengths—measured in character changes—are an essential requirement of clock-based divergence estimation, regardless of whether the fossil calibrations used represent nodes or tips. However, a separate set of divergence time approaches are typically used to date palaeontological trees, which may lack such branch lengths. Among these methods, sophisticated probabilistic approaches have recently emerged, in contrast with simpler algorithms relying on minimum node ages. Here, using a novel phylogenetic hypothesis for Mesozoic dinosaurs, we apply two such approaches to estimate divergence times for: (i) Dinosauria, (ii) Avialae (the earliest birds) and (iii) Neornithes (crown birds). We find: (i) the plausibility of a Permian origin for dinosaurs to be dependent on whether Nyasasaurus is the oldest dinosaur, (ii) a Middle to Late Jurassic origin of avian flight regardless of whether Archaeopteryx or Aurornis is considered the first bird and (iii) a Late Cretaceous origin for Neornithes that is broadly congruent with other node- and tip-dating estimates. Demonstrating the feasibility of probabilistic time-scaling further opens up divergence estimation to the rich histories of extinct biodiversity in the fossil record, even in the absence of detailed character data.


PLoS ONE ◽  
2011 ◽  
Vol 6 (11) ◽  
pp. e27138 ◽  
Author(s):  
Sebastián Duchêne ◽  
Frederick I. Archer ◽  
Julia Vilstrup ◽  
Susana Caballero ◽  
Phillip A. Morin

2019 ◽  
Vol 69 (4) ◽  
pp. 660-670 ◽  
Author(s):  
Tom Carruthers ◽  
Michael J Sanderson ◽  
Robert W Scotland

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.]


2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Yan Du ◽  
Shaoyuan Wu ◽  
Scott V. Edwards ◽  
Liang Liu

Abstract Background The flood of genomic data to help build and date the tree of life requires automation at several critical junctures, most importantly during sequence assembly and alignment. It is widely appreciated that automated alignment protocols can yield inaccuracies, but the relative impact of various sources error on phylogenomic analysis is not yet known. This study employs an updated mammal data set of 5162 coding loci sampled from 90 species to evaluate the effects of alignment uncertainty, substitution models, and fossil priors on gene tree, species tree, and divergence time estimation. Additionally, a novel coalescent likelihood ratio test is introduced for comparing competing species trees against a given set of gene trees. Results The aligned DNA sequences of 5162 loci from 90 species were trimmed and filtered using trimAL and two filtering protocols. The final dataset contains 4 sets of alignments - before trimming, after trimming, filtered by a recently proposed pipeline, and further filtered by comparing ML gene trees for each locus with the concatenation tree. Our analyses suggest that the average discordance among the coalescent trees is significantly smaller than that among the concatenation trees estimated from the 4 sets of alignments or with different substitution models. There is no significant difference among the divergence times estimated with different substitution models. However, the divergence dates estimated from the alignments after trimming are more recent than those estimated from the alignments before trimming. Conclusions Our results highlight that alignment uncertainty of the updated mammal data set and the choice of substitution models have little impact on tree topologies yielded by coalescent methods for species tree estimation, whereas they are more influential on the trees made by concatenation. Given the choice of calibration scheme and clock models, divergence time estimates are robust to the choice of substitution models, but removing alignments deemed problematic by trimming algorithms can lead to more recent dates. Although the fossil prior is important in divergence time estimation, Bayesian estimates of divergence times in this data set are driven primarily by the sequence data.


2020 ◽  
Vol 111 (6) ◽  
pp. 573-582
Author(s):  
Zachary B Hancock ◽  
Heath Blackmon

Abstract Isolation-by-distance is a widespread pattern in nature that describes the reduction of genetic correlation between subpopulations with increased geographic distance. In the population ancestral to modern sister species, this pattern may hypothetically inflate population divergence time estimation due to allele frequency differences in subpopulations at the ends of the ancestral population. In this study, we analyze the relationship between the time to the most recent common ancestor and the population divergence time when the ancestral population model is a linear stepping-stone. Using coalescent simulations, we compare the coalescent time to the population divergence time for various ratios of the divergence time over the population size. Next, we simulate whole genomes to obtain single nucleotide polymorphisms (SNPs), and use the Bayesian coalescent program SNAPP to estimate divergence times. We find that as the rate of migration between neighboring demes decreases, the coalescent time becomes significantly greater than the population divergence time when sampled from end demes. Divergence-time overestimation in SNAPP becomes severe when the divergence-to-population size ratio < 10 and migration is low. Finally, we demonstrate the impact of ancestral isolation-by-distance on divergence-time estimation using an empirical dataset of squamates (Tropidurus) endemic to Brazil. We conclude that studies estimating divergence times should be cognizant of the potential ancestral population structure in an explicitly spatial context or risk dramatically overestimating the timing of population splits.


2016 ◽  
Vol 371 (1699) ◽  
pp. 20150141 ◽  
Author(s):  
Hui-Jie Lee ◽  
Hirohisa Kishino ◽  
Nicolas Rodrigue ◽  
Jeffrey L. Thorne

Different types of nucleotide substitutions experience different patterns of rate change over time. We propose clustering context-dependent (or context-independent) nucleotide substitution types according to how their rates change and then using the grouping for divergence time estimation. With our models, relative rates among types that are in the same group are fixed, whereas absolute rates of the types within a group change over time according to a shared relaxed molecular clock. We illustrate our procedure by analysing a 0.15 Mb intergenic region to infer divergence times relating eight primates. The different groupings of substitution types that we explore have little effect on the posterior means of divergence times, but the widths of the credibility intervals decrease as the number of groups increases. This article is part of the themed issue ‘Dating species divergences using rocks and clocks’.


2018 ◽  
Author(s):  
Joëlle Barido-Sottani ◽  
Gabriel Aguirre-Fernández ◽  
Melanie Hopkins ◽  
Tanja Stadler ◽  
Rachel Warnock

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.


2015 ◽  
Vol 282 (1798) ◽  
pp. 20141013 ◽  
Author(s):  
Rachel C. M. Warnock ◽  
James F. Parham ◽  
Walter G. Joyce ◽  
Tyler R. Lyson ◽  
Philip C. J. Donoghue

Calibration is the rate-determining step in every molecular clock analysis and, hence, considerable effort has been expended in the development of approaches to distinguish good from bad calibrations. These can be categorized into a priori evaluation of the intrinsic fossil evidence, and a posteriori evaluation of congruence through cross-validation. We contrasted these competing approaches and explored the impact of different interpretations of the fossil evidence upon Bayesian divergence time estimation. The results demonstrate that a posteriori approaches can lead to the selection of erroneous calibrations. Bayesian posterior estimates are also shown to be extremely sensitive to the probabilistic interpretation of temporal constraints. Furthermore, the effective time priors implemented within an analysis differ for individual calibrations when employed alone and in differing combination with others. This compromises the implicit assumption of all calibration consistency methods, that the impact of an individual calibration is the same when used alone or in unison with others. Thus, the most effective means of establishing the quality of fossil-based calibrations is through a priori evaluation of the intrinsic palaeontological, stratigraphic, geochronological and phylogenetic data. However, effort expended in establishing calibrations will not be rewarded unless they are implemented faithfully in divergence time analyses.


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