scholarly journals Evaluating the Adequacy of Molecular Clock Models Using Posterior Predictive Simulations

2015 ◽  
Vol 32 (11) ◽  
pp. 2986-2995 ◽  
Author(s):  
David A. Duchêne ◽  
Sebastian Duchêne ◽  
Edward C. Holmes ◽  
Simon Y.W. Ho
Keyword(s):  
Molecular Clock ◽  
Clock Models ◽  
Predictive Simulations

scholarly journals Biogeographic calibrations for the molecular clock

2015 ◽  
Vol 11 (9) ◽  
pp. 20150194 ◽  
Author(s):  
Simon Y. W. Ho ◽  
K. Jun Tong ◽  
Charles S. P. Foster ◽  
Andrew M. Ritchie ◽  
Nathan Lo ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Temporal Information ◽  
Rate Variation ◽  
Molecular Clocks ◽  
Climatic Data ◽  
Absolute Time ◽  
Biological Studies ◽  
Clock Models

Molecular estimates of evolutionary timescales have an important role in a range of biological studies. Such estimates can be made using methods based on molecular clocks, including models that are able to account for rate variation across lineages. All clock models share a dependence on calibrations, which enable estimates to be given in absolute time units. There are many available methods for incorporating fossil calibrations, but geological and climatic data can also provide useful calibrations for molecular clocks. However, a number of strong assumptions need to be made when using these biogeographic calibrations, leading to wide variation in their reliability and precision. In this review, we describe the nature of biogeographic calibrations and the assumptions that they involve. We present an overview of the different geological and climatic events that can provide informative calibrations, and explain how such temporal information can be incorporated into dating analyses.

scholarly journals Additive Uncorrelated Relaxed Clock Models for the Dating of Genomic Epidemiology Phylogenies

2020 ◽  
Vol 38 (1) ◽  
pp. 307-317
Author(s):  
Xavier Didelot ◽  
Igor Siveroni ◽  
Erik M Volz
Keyword(s):  
Molecular Clock ◽  
Real Data ◽  
Evolutionary Rates ◽  
Data Sets ◽  
Clock Rate ◽  
Clock Model ◽  
Genomic Epidemiology ◽  
Molecular Clock Model ◽  
Clock Models ◽  
Relaxed Clock

Abstract Phylogenetic dating is one of the most powerful and commonly used methods of drawing epidemiological interpretations from pathogen genomic data. Building such trees requires considering a molecular clock model which represents the rate at which substitutions accumulate on genomes. When the molecular clock rate is constant throughout the tree then the clock is said to be strict, but this is often not an acceptable assumption. Alternatively, relaxed clock models consider variations in the clock rate, often based on a distribution of rates for each branch. However, we show here that the distributions of rates across branches in commonly used relaxed clock models are incompatible with the biological expectation that the sum of the numbers of substitutions on two neighboring branches should be distributed as the substitution number on a single branch of equivalent length. We call this expectation the additivity property. We further show how assumptions of commonly used relaxed clock models can lead to estimates of evolutionary rates and dates with low precision and biased confidence intervals. We therefore propose a new additive relaxed clock model where the additivity property is satisfied. We illustrate the use of our new additive relaxed clock model on a range of simulated and real data sets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.

scholarly journals Divergence dating using mixed effects clock modelling: An application to HIV-1

2019 ◽  
Vol 5 (2) ◽  
Author(s):  
Magda Bletsa ◽  
Marc A Suchard ◽  
Xiang Ji ◽  
Sophie Gryseels ◽  
Bram Vrancken ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Mixed Effects ◽  
Recent Common Ancestor ◽  
Rate Variation ◽  
Clock Model ◽  
Data Set ◽  
Genome Data ◽  
Most Recent Common Ancestor ◽  
Clock Models ◽  
Hiv 1

Abstract The need to estimate divergence times in evolutionary histories in the presence of various sources of substitution rate variation has stimulated a rich development of relaxed molecular clock models. Viral evolutionary studies frequently adopt an uncorrelated clock model as a generic relaxed molecular clock process, but this may impose considerable estimation bias if discrete rate variation exists among clades or lineages. For HIV-1 group M, rate variation among subtypes has been shown to result in inconsistencies in time to the most recent common ancestor estimation. Although this calls into question the adequacy of available molecular dating methods, no solution to this problem has been offered so far. Here, we investigate the use of mixed effects molecular clock models, which combine both fixed and random effects in the evolutionary rate, to estimate divergence times. Using simulation, we demonstrate that this model outperforms existing molecular clock models in a Bayesian framework for estimating time-measured phylogenies in the presence of mixed sources of rate variation, while also maintaining good performance in simpler scenarios. By analysing a comprehensive HIV-1 group M complete genome data set we confirm considerable rate variation among subtypes that is not adequately modelled by uncorrelated relaxed clock models. The mixed effects clock model can accommodate this rate variation and results in a time to the most recent common ancestor of HIV-1 group M of 1920 (1915–25), which is only slightly earlier than the uncorrelated relaxed clock estimate for the same data set. The use of complete genome data appears to have a more profound impact than the molecular clock model because it reduces the credible intervals by 50 per cent relative to similar estimates based on short envelope gene sequences.

scholarly journals The emergence of SARS-CoV-2 variants of concern is driven by acceleration of the evolutionary rate

2021 ◽  
Author(s):  
John H Tay ◽  
Ashleigh F Porter ◽  
Wytamma Wirth ◽  
Sebastian Duchene
Keyword(s):  
Molecular Evolution ◽  
Genome Sequence ◽  
Molecular Clock ◽  
Evolutionary Rate ◽  
Sequence Data ◽  
Rate Estimate ◽  
Genome Sequence Data ◽  
Genome Data ◽  
Phylogenetic Level ◽  
Clock Models

The ongoing SARS-CoV-2 pandemic has seen an unprecedented amount of rapidly generated genome data. These data have revealed the emergence of lineages with mutations associated to transmissibility and antigenicity, known as variants of concern (VOCs). A striking aspect of VOCs is that many of them involve an unusually large number of defining mutations. Current phylogenetic estimates of the evolutionary rate of SARS-CoV-2 suggest that its genome accrues around 2 mutations per month. However, VOCs can have around 15 defining mutations and it is hypothesised that they emerged over the course of a few months, implying that they must have evolved faster for a period of time. We analysed genome sequence data from the GISAID database to assess whether the emergence of VOCs can be attributed to changes in the evolutionary rate of the virus and whether this pattern can be detected at a phylogenetic level using genome data. We fit a range of molecular clock models and assessed their statistical fit. Our analyses indicate that the emergence of VOCs is driven by an episodic increase in the evolutionary rate of around 4-fold the background phylogenetic rate estimate that may have lasted several weeks or months. These results underscore the importance of monitoring the molecular evolution of the virus as a means of understanding the circumstances under which VOCs may emerge.

scholarly journals A General Comparison of Relaxed Molecular Clock Models

2007 ◽  
Vol 24 (12) ◽  
pp. 2669-2680 ◽  
Author(s):  
T. Lepage ◽  
D. Bryant ◽  
H. Philippe ◽  
N. Lartillot
Keyword(s):  
Molecular Clock ◽  
Clock Models ◽  
Relaxed Molecular Clock

scholarly journals Response to Comment on “The Placental Mammal Ancestor and the Post–K-Pg Radiation of Placentals”

Science ◽  
2013 ◽  
Vol 341 (6146) ◽  
pp. 613.3-613 ◽  
Author(s):  
Maureen A. O’Leary ◽  
Jonathan I. Bloch ◽  
John J. Flynn ◽  
Timothy J. Gaudin ◽  
Andres Giallombardo ◽  
...  
Keyword(s):  
Molecular Clock ◽  
Explanatory Power ◽  
Placental Mammal ◽  
Substitution Rates ◽  
Power Application ◽  
Tree Building ◽  
Diverse Data ◽  
Clock Models

Tree-building with diverse data maximizes explanatory power. Application of molecular clock models to ancient speciation events risks a bias against detection of fast radiations subsequent to the Cretaceous-Paleogene (K-Pg) event. Contrary to Springer et al., post–K-Pg placental diversification does not require “virus-like” substitution rates. Even constraining clade ages to their model, the explosive model best explains placental evolution.

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