Additive uncorrelated relaxed clock models for the dating of genomic epidemiology phylogenies
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Published version
Author(s)
Didelot, Xavier
Siveroni, Igor
Volz, Erik M
Type
Journal Article
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.
Date Issued
2021-01
Date Acceptance
2020-07-20
Citation
Molecular Biology and Evolution, 2021, 38 (1), pp.307-317
ISSN
0737-4038
Publisher
Oxford University Press (OUP)
Start Page
307
End Page
317
Journal / Book Title
Molecular Biology and Evolution
Volume
38
Issue
1
Copyright Statement
©The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work isproperly cited.
License URL
Sponsor
Medical Research Council (MRC)
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/32722797
PII: 5877436
Grant Number
MR/R015600/1
Subjects
clock model
dated phylogeny
genomic epidemiology
Evolutionary Biology
0601 Biochemistry and Cell Biology
0603 Evolutionary Biology
0604 Genetics
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2020-07-28