Inferring the Probability of the Derived vs the Ancestral Allelic State at a Polymorphic Site

Genetics
Peter D Keightley, Benjamin C Jackson

Abstract

It is known that the allele ancestral to the variation at a polymorphic site cannot be assigned with certainty, and that the most frequently used method to assign the ancestral state-maximum parsimony-is prone to misinference. Estimates of counts of sites that have a certain number of copies of the derived allele in a sample (the unfolded site frequency spectrum, uSFS) made by parsimony are therefore also biased. We previously developed a maximum likelihood method to estimate the uSFS for a focal species using information from two outgroups while assuming simple models of nucleotide substitution. Here, we extend this approach to allow multiple outgroups (implemented for three outgroups), potentially any phylogenetic tree topology, and more complex models of nucleotide substitution. We find, however, that two outgroups and the Kimura two-parameter model are adequate for uSFS inference in most cases. We show that using parsimony to infer the ancestral state at a specific site seriously breaks down in two situations. The first is where the outgroups provide no information about the ancestral state of variation in the focal species. In this case, nucleotide variation will be underestimated if such sites are excluded. The second is ...Continue Reading

References

Jan 1, 1981·Journal of Molecular Evolution·J Felsenstein
Dec 16, 1998·Journal of Molecular Evolution·A Eyre-Walker
Jul 6, 2000·Genetics·J C Fay, C I Wu
Sep 9, 2000·Genetics·M W Nachman, S L Crowell
Aug 26, 2003·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Peter F ArndtTerence Hwa
Dec 12, 2003·Genetics·Emmanuelle Baudry, Frantz Depaulis
Feb 24, 2006·PLoS Biology·Benjamin F VoightJonathan K Pritchard
May 8, 2007·Molecular Biology and Evolution·Ziheng Yang
Jun 5, 2007·Molecular Biology and Evolution·Ryan D HernandezCarlos D Bustamante
Jun 3, 2008·PLoS Genetics·Adam R BoykoCarlos D Bustamante
Oct 29, 2010·Nature·Gonçalo R AbecasisGil A McVean
Jun 8, 2012·Genetics·Charles H LangleyDavid J Begun
Oct 4, 2015·Nature·UNKNOWN 1000 Genomes Project ConsortiumGonçalo R Abecasis
Nov 8, 2015·G3 : Genes - Genomes - Genetics·Melinda A Yang, Montgomery Slatkin
Apr 26, 2017·ELife·Kelley Harris, Jonathan K Pritchard

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Citations

Nov 9, 2019·G3 : Genes - Genomes - Genetics·Michael LynchTakahiro Maruki
May 18, 2020·Genetics·Tuomas Hämälä, Peter Tiffin
Aug 22, 2018·Proceedings of the National Academy of Sciences of the United States of America·Dorothy E LoyBeatrice H Hahn
Jan 17, 2021·Nature Plants·Roberto LozanoMichael A Gore
Sep 4, 2019·Nature Genetics·Jerome KelleherGil McVean
Nov 24, 2019·BMC Bioinformatics·Luis ToradaMatteo Fumagalli
Aug 21, 2020·Virus Evolution·Oscar A MacLeanDavid L Robertson
Apr 2, 2021·The Plant Cell·Rory J CraigPeter D Keightley
Jan 6, 2021·Nature Communications·Myung-Shin KimSoon-Chun Jeong
Sep 10, 2021·Molecular Biology and Evolution·Robert HorvathTanja Slotte
Dec 4, 2021·Communications Biology·Ruidong XiangMichael E Goddard

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Software Mentioned

WGAbed
PAML
MANY
EPO
Ensembl

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