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Estimating time to the common ancestor for a beneficial allele

Joel Smith, Graham Coop, Matthew Stephens, John Novembre
doi: https://doi.org/10.1101/071241
Joel Smith
1Department of Ecology and Evolution, University of Chicago, Chicago, Illinois, United States of America
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Graham Coop
2Center for Population Biology, Department of Evolution and Ecology, University of California, Davis, California, United States of America
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Matthew Stephens
3Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America
4Department of Statistics, University of Chicago, Chicago, Illinois, United States of America
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John Novembre
3Department of Human Genetics, University of Chicago, Chicago, Illinois, United States of America
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Abstract

The haplotypes of a beneficial allele carry information about its history that can shed light on its age and putative cause for its increase in frequency. Specifically, the signature of an allele’s age is contained in the pattern of local ancestry that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to provide a global perspective on the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans.

Footnotes

  • ↵* jnovembre{at}uchicago.edu

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 August 24, 2016.
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Estimating time to the common ancestor for a beneficial allele
Joel Smith, Graham Coop, Matthew Stephens, John Novembre
bioRxiv 071241; doi: https://doi.org/10.1101/071241
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Estimating time to the common ancestor for a beneficial allele
Joel Smith, Graham Coop, Matthew Stephens, John Novembre
bioRxiv 071241; doi: https://doi.org/10.1101/071241

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