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The effect of genetic structure on molecular dating and tests for temporal signal

Murray, Gemma G.R.; Murray, Gemma G. R.; Murray, Gemma G. R.; Wang, Fang; Harrison, Ewan M.; Paterson, Gavin K.; Mather, Alison E.; Harris, Simon R.; Holmes, Mark A.; Rambaut, Andrew; Welch, John J.

Authors

Gemma G.R. Murray

Gemma G. R. Murray

Gemma G. R. Murray

Fang Wang

Ewan M. Harrison

Gavin K. Paterson

Alison E. Mather

Simon R. Harris

Mark A. Holmes

Andrew Rambaut

John J. Welch



Contributors

M. Gilbert
Editor

Abstract

© 2016 British Ecological Society. 'Dated-tip' methods of molecular dating use DNA sequences sampled at different times, to estimate the age of their most recent common ancestor. Several tests of 'temporal signal' are available to determine whether data sets are suitable for such analysis. However, it remains unclear whether these tests are reliable. We investigate the performance of several tests of temporal signal, including some recently suggested modifications. We use simulated data (where the true evolutionary history is known), and whole genomes of methicillin-resistant Staphylococcus aureus (to show how particular problems arise with real-world data sets). We show that all of the standard tests of temporal signal are seriously misleading for data where temporal and genetic structures are confounded (i.e. where closely related sequences are more likely to have been sampled at similar times). This is not an artefact of genetic structure or tree shape per se, and can arise even when sequences have measurably evolved during the sampling period. More positively, we show that a 'clustered permutation' approach introduced by Duchêne et al. (Molecular Biology and Evolution, 32, 2015, 1895) can successfully correct for this artefact in all cases and introduce techniques for implementing this method with real data sets. The confounding of temporal and genetic structures may be difficult to avoid in practice, particularly for outbreaks of infectious disease, or when using ancient DNA. Therefore, we recommend the use of 'clustered permutation' for all analyses. The failure of the standard tests may explain why different methods of dating pathogen origins have reached such wildly different conclusions.

Journal Article Type Article
Publication Date 2016-01
Journal Methods in ecology and evolution
Print ISSN 2041-210X
Electronic ISSN 2041-210X
Publisher Wiley
Peer Reviewed Peer Reviewed
Volume 7
Issue 1
Pages 80-89
Institution Citation Murray, G. G., Wang, F., Harrison, E. M., Paterson, G. K., Mather, A. E., Harris, S. R., …Welch, J. J. (2016). The effect of genetic structure on molecular dating and tests for temporal signal. Methods in ecology and evolution British Ecological Society, 7(1), 80-89. doi:10.1111/2041-210x.12466
DOI https://doi.org/10.1111/2041-210x.12466
Keywords Bayesian dating, Dated-tips, Pathogen origins, Permutation tests, Staphylococcus aureus
Publisher URL http://onlinelibrary.wiley.com/doi/10.1111/2041-210X.12466/abstract;jsessionid=56E9DA16960FA7CCA2F7EF285FC135A2.f02t01
Copyright Statement © 2015 The Authors. Methods in Ecology and Evolution published by John Wiley & Sons Ltd on behalf of British Ecological Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Additional Information This is an open access article : Murray, G. G. R., Wang, F., Harrison, E. M., Paterson, G. K., Mather, A. E., Harris, S. R., Holmes, M. A., Rambaut, A., Welch, J. J. (2016), The effect of genetic structure on molecular dating and tests for temporal signal. Methods in Ecology and Evolution, 7: 80–89. doi: 10.1111/2041-210X.12466

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Copyright Statement
© 2015 The Authors. Methods in Ecology and Evolution published by John Wiley & Sons Ltd on behalf of British Ecological Society.

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.



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