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Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies
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Didelot, Xavier, Siveroni, Igor and Volz, Erik M. (2021) Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies. Molecular Biology and Evolution, 38 (1). pp. 307-317. msaa193. doi:10.1093/molbev/msaa193 ISSN 1537-1719.
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Official URL: https://doi.org/10.1093/molbev/msaa193
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 neighbouring 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 datasets, and we show that using this new model leads to more accurate estimates of mean evolutionary rates and ancestral dates.
Item Type: | Journal Article | ||||||||
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Subjects: | Q Science > QH Natural history > QH426 Genetics | ||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
SWORD Depositor: | Library Publications Router | ||||||||
Library of Congress Subject Headings (LCSH): | Phylogeny, Biology -- Classification, Evolutionary genetics -- Mathematics, Bayesian statistical decision theory | ||||||||
Journal or Publication Title: | Molecular Biology and Evolution | ||||||||
Publisher: | Oxford University Press (OUP) | ||||||||
ISSN: | 1537-1719 | ||||||||
Official Date: | January 2021 | ||||||||
Dates: |
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Volume: | 38 | ||||||||
Number: | 1 | ||||||||
Page Range: | pp. 307-317 | ||||||||
Article Number: | msaa193 | ||||||||
DOI: | 10.1093/molbev/msaa193 | ||||||||
Status: | Peer Reviewed | ||||||||
Publication Status: | Published | ||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||
Date of first compliant deposit: | 6 August 2020 | ||||||||
Date of first compliant Open Access: | 7 August 2020 | ||||||||
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