title: Estimating the Ages of Selection Signals from Different Epochs in Human History.
abstract: Genetic variation harbors signatures of natural selection driven by selective pressures that are often unknown. Estimating the ages of selection signals may allow reconstructing the history of environmental changes that shaped human phenotypes and diseases. We have developed an approximate Bayesian computation (ABC) approach to estimate allele ages under a model of selection on new mutations and under demographic models appropriate for human populations. We have applied it to two resequencing data sets: An ultra-high depth data set from a relatively small sample of unrelated individuals and a lower depth data set in a larger sample with transmission information. In addition to evaluating the accuracy of our method based on simulations, for each SNP, we assessed the consistency between the posterior probabilities estimated by the ABC approach and the ancient DNA record, finding good agreement between the two types of data and methods. Applying this ABC approach to data for eight single nucleotide polymorphisms (SNPs), we were able to rule out an onset of selection prior to the dispersal out-of-Africa for three of them and more recent than the spread of agriculture for an additional three SNPs.
authors.affiliation: Department of Human Genetics, University of Chicago.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakagome
authors.affiliation: Department of Human Genetics, University of Chicago.
authors.forename: Gorka
authors.initials: G
authors.lastname: Alkorta-Aranburu
authors.affiliation: Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford, United Kingdom.
authors.forename: Roberto
authors.initials: R
authors.lastname: Amato
authors.affiliation: Department of Human Genetics, University of Chicago.
authors.forename: Bryan
authors.initials: B
authors.lastname: Howie
authors.affiliation: Department of Human Genetics, University of Chicago.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Peter
authors.affiliation: Department of Human Genetics, University of Chicago Department of Ecology and Evolution, University of Chicago dirienzo@bsd.uchicago.edu rr-hudson@uchicago.edu.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Hudson
authors.affiliation: Department of Human Genetics, University of Chicago dirienzo@bsd.uchicago.edu rr-hudson@uchicago.edu.
authors.forename: Anna
authors.initials: A
authors.lastname: Di Rienzo
mesh_terms: D000483:Alleles; D001499:Bayes Theorem; D019295:Computational Biology / Q000379:methods; D003198:Computer Simulation; D019143:Evolution, Molecular; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D006801:Humans; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
keywords: approximate Bayesian computation; autoimmune disease; onset of selection; selective pressures