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

1. ‘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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832290/
https://www.ncbi.nlm.nih.gov/pubmed/27110344
http://dx.doi.org/10.1111/2041-210X.12466
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author 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.
author_facet 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.
author_sort Murray, Gemma G. R.
collection PubMed
description 1. ‘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. 2. 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). 3. 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. 4. 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.
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spelling pubmed-48322902016-04-20 The effect of genetic structure on molecular dating and tests for temporal signal 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. Methods Ecol Evol Population Genetics and Evolution 1. ‘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. 2. 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). 3. 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. 4. 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. John Wiley and Sons Inc. 2015-09-22 2016-01 /pmc/articles/PMC4832290/ /pubmed/27110344 http://dx.doi.org/10.1111/2041-210X.12466 Text en © 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 (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Population Genetics and Evolution
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.
The effect of genetic structure on molecular dating and tests for temporal signal
title The effect of genetic structure on molecular dating and tests for temporal signal
title_full The effect of genetic structure on molecular dating and tests for temporal signal
title_fullStr The effect of genetic structure on molecular dating and tests for temporal signal
title_full_unstemmed The effect of genetic structure on molecular dating and tests for temporal signal
title_short The effect of genetic structure on molecular dating and tests for temporal signal
title_sort effect of genetic structure on molecular dating and tests for temporal signal
topic Population Genetics and Evolution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832290/
https://www.ncbi.nlm.nih.gov/pubmed/27110344
http://dx.doi.org/10.1111/2041-210X.12466
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