MBE Advance Access originally published online on September 21, 2007
Molecular Biology and Evolution 2007 24(12):2669-2680; doi:10.1093/molbev/msm193
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Research Articles |
A General Comparison of Relaxed Molecular Clock Models
* Department of Mathematics and Statistics, McGill University, Montréal, Québec, Canada
Department of Mathematics, University of Auckland, New Zealand
Département de biochimie, Université de Montréal, Québec, Canada
Laboratoire d'Informatique, de Robotique et de Microélectronique de Montpellier, UMR 5506, CNRS-Université de Montpellier 2, 161, rue Ada, 34392 Montpellier Cedex 5, France
E-mail: nicolas.lartillot{at}lirmm.fr.
Accepted for publication September 7, 2007.
Several models have been proposed to relax the molecular clock in order to estimate divergence times. However, it is unclear which model has the best fit to real data and should therefore be used to perform molecular dating. In particular, we do not know whether rate autocorrelation should be considered or which prior on divergence times should be used. In this work, we propose a general bench mark of alternative relaxed clock models. We have reimplemented most of the already existing models, including the popular lognormal model, as well as various prior choices for divergence times (birth–death, Dirichlet, uniform), in a common Bayesian statistical framework. We also propose a new autocorrelated model, called the "CIR" process, with well-defined stationary properties. We assess the relative fitness of these models and priors, when applied to 3 different protein data sets from eukaryotes, vertebrates, and mammals, by computing Bayes factors using a numerical method called thermodynamic integration. We find that the 2 autocorrelated models, CIR and lognormal, have a similar fit and clearly outperform uncorrelated models on all 3 data sets. In contrast, the optimal choice for the divergence time prior is more dependent on the data investigated. Altogether, our results provide useful guidelines for model choice in the field of molecular dating while opening the way to more extensive model comparisons.
Key Words: relaxed clock • Bayes factor • molecular dating • CIR process • phylogeny • Markov chain Monte Carlo
Spencer Muse, Associate Editor