title: A test for ancient selective sweeps and an application to candidate sites in modern humans.
abstract: We introduce a new method to detect ancient selective sweeps centered on a candidate site. We explored different patterns produced by sweeps around a fixed beneficial mutation, and found that a particularly informative statistic measures the consistency between majority haplotypes near the mutation and genotypic data from a closely related population. We incorporated this statistic into an approximate Bayesian computation (ABC) method that tests for sweeps at a candidate site. We applied this method to simulated data and show that it has some power to detect sweeps that occurred more than 10,000 generations in the past. We also applied it to 1,000 Genomes and Complete Genomics data combined with high-coverage Denisovan and Neanderthal genomes to test for sweeps in modern humans since the separation from the Neanderthal-Denisovan ancestor. We tested sites at which humans are fixed for the derived (i.e., nonchimpanzee allele) whereas the Neanderthal and Denisovan genomes are homozygous for the ancestral allele. We observe only weak differences in statistics indicative of selection between functional categories. When we compare patterns of scaled diversity or use our ABC approach, we fail to find a significant difference in signals of classic selective sweeps between regions surrounding nonsynonymous and synonymous changes, but we detect a slight enrichment for reduced scaled diversity around splice site changes. We also present a list of candidate sites that show high probability of having undergone a classic sweep in the modern human lineage since the split from Neanderthals and Denisovans.
authors.affiliation: Department of Integrative Biology, University of California, Berkeley Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany fernandoracimo@gmail.com.
authors.forename: Fernando
authors.initials: F
authors.lastname: Racimo
authors.affiliation: Department of Evolutionary Genetics, Max Planck Institute for Evolutionary Anthropology, Leipzig, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuhlwilm
authors.affiliation: Department of Integrative Biology, University of California, Berkeley.
authors.forename: Montgomery
authors.initials: M
authors.lastname: Slatkin
mesh_terms: D000818:Animals; D001499:Bayes Theorem; D019143:Evolution, Molecular; D015894:Genome, Human; D006801:Humans; D008957:Models, Genetic; D059125:Neanderthals / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012641:Selection, Genetic
keywords: Denisova; Neanderthal; approximate Bayesian computation; modern humans; selective sweeps