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Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses

Mahan Ghafari, View ORCID ProfilePeter Simmonds, Oliver G Pybus, Aris Katzourakis
doi: https://doi.org/10.1101/2021.02.09.430479
Mahan Ghafari
1Department of Zoology, University of Oxford
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Peter Simmonds
2Nuffield Department of Medicine, University of Oxford
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Oliver G Pybus
1Department of Zoology, University of Oxford
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Aris Katzourakis
1Department of Zoology, University of Oxford
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  • For correspondence: aris.katzourakis@zoo.ox.ac.uk
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Abstract

Molecular clock dating is widely used to estimate timescales of phylogenetic histories and to infer rates at which species evolve. One of the major challenges with inferring rates of molecular evolution is the observation of a strong correlation between estimated rates and the timeframe of their measurements. Recent empirical analysis of virus evolutionary rates suggest that a power-law rate decay best explains the time-dependent pattern of substitution rates and that the same pattern is observed regardless of virus type (e.g. groups I-VII in the Baltimore classification). However there exists no explanation for this trend based on molecular evolutionary mechanisms. We provide a simple predictive mechanistic model of the time-dependent rate phenomenon, incorporating saturation and host constraints on the evolution of some sites. Our model recapitulates the ubiquitous power-law rate decay with a slope of −0.65 (95% HPD: −0.72, −0.52) and can satisfactorily account for the variation in inferred molecular evolutionary rates over a wide range of timeframes. We show that once the saturation of sites starts - typically after hundreds of years in RNA viruses and thousands of years in DNA viruses - standard substitution models fail to correctly estimate divergence times among species, while our model successfully re-creates the observed pattern of rate decay. We apply our model to re-date the diversification of genotypes of hepatitis C virus (HCV) to 396,000 (95% HPD: 326,000 - 425,000) years before present, a time preceding the dispersal of modern humans out of Africa, and also showed that the most recent common ancestor of sarbecoviruses dates back to 23,500 (95% HPD: 21,100 - 25,300) years ago, nearly thirty times older than previous estimates. This not only creates a radical new perspective for our understanding the origins of HCV but also suggests a substantial revision of evolutionary timescales of other viruses can be similarly achieved.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵* E-mail: aris.katzourakis{at}zoo.ox.ac.uk

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted February 09, 2021.
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Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses
Mahan Ghafari, Peter Simmonds, Oliver G Pybus, Aris Katzourakis
bioRxiv 2021.02.09.430479; doi: https://doi.org/10.1101/2021.02.09.430479
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Prisoner of War dynamics explains the time-dependent pattern of substitution rates in viruses
Mahan Ghafari, Peter Simmonds, Oliver G Pybus, Aris Katzourakis
bioRxiv 2021.02.09.430479; doi: https://doi.org/10.1101/2021.02.09.430479

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