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Mol Ecol. 2016 May;25(9):1911-24. doi: 10.1111/mec.13586. Epub 2016 Apr 20.

Inferences from tip-calibrated phylogenies: a review and a practical guide.

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Department of Genetics, Evolution and Environment, UCL Genetics Institute, University College London, Gower Street, London, WC1E 6BT, UK.


Molecular dating of phylogenetic trees is a growing discipline using sequence data to co-estimate the timing of evolutionary events and rates of molecular evolution. All molecular-dating methods require converting genetic divergence between sequences into absolute time. Historically, this could only be achieved by associating externally derived dates obtained from fossil or biogeographical evidence to internal nodes of the tree. In some cases, notably for fast-evolving genomes such as viruses and some bacteria, the time span over which samples were collected may cover a significant proportion of the time since they last shared a common ancestor. This situation allows phylogenetic trees to be calibrated by associating sampling dates directly to the sequences representing the tips (terminal nodes) of the tree. The increasing availability of genomic data from ancient DNA extends the applicability of such tip-based calibration to a variety of taxa including humans, extinct megafauna and various microorganisms which typically have a scarce fossil record. The development of statistical models accounting for heterogeneity in different aspects of the evolutionary process while accommodating very large data sets (e.g. whole genomes) has allowed using tip-dating methods to reach inferences on divergence times, substitution rates, past demography or the age of specific mutations on a variety of spatiotemporal scales. In this review, we summarize the current state of the art of tip dating, discuss some recent applications, highlight common pitfalls and provide a 'how to' guide to thoroughly perform such analyses.


Bayesian phylogenetics; calibration, divergence time and substitution rate inferences; measurably evolving populations; population dynamics; tip-dating

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