title: Demography-adjusted tests of neutrality based on genome-wide SNP data.
abstract: Tests of the neutral evolution hypothesis are usually built on the standard null model which assumes that mutations are neutral and the population size remains constant over time. However, it is unclear how such tests are affected if the last assumption is dropped. Here, we extend the unifying framework for tests based on the site frequency spectrum, introduced by Achaz and Ferretti, to populations of varying size. Key ingredients are the first two moments of the site frequency spectrum. We show how these moments can be computed analytically if a population has experienced two instantaneous size changes in the past. We apply our method to data from ten human populations gathered in the 1000 genomes project, estimate their demographies and define demography-adjusted versions of Tajima's D, Fay & Wu's H, and Zeng's E. Our results show that demography-adjusted test statistics facilitate the direct comparison between populations and that most of the differences among populations seen in the original unadjusted tests can be explained by their underlying demographies. Upon carrying out whole-genome screens for deviations from neutrality, we identify candidate regions of recent positive selection. We provide track files with values of the adjusted and unadjusted tests for upload to the UCSC genome browser.
authors.affiliation: Department of Physics, University of Gothenburg, SE-412 96 Gothenburg, Sweden; The Linnaeus Centre for Marine Evolutionary Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Rafajlović
authors.affiliation: Institut für Genetik, Universität zu Köln, 50674 Köln, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Klassmann
authors.affiliation: Department of Zoology, University of Cambridge, CB2 3EJ Cambridge, UK; Integrative Systems Biology Lab, King Abdullah University of Science and Technology, Thuwal 23955-6900, Saudi Arabia.
authors.forename: A
authors.initials: A
authors.lastname: Eriksson
authors.affiliation: Institut für Genetik, Universität zu Köln, 50674 Köln, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Wiehe
authors.affiliation: Department of Physics, University of Gothenburg, SE-412 96 Gothenburg, Sweden; The Linnaeus Centre for Marine Evolutionary Biology, University of Gothenburg, SE-405 30 Gothenburg, Sweden. Electronic address: Bernhard.Mehlig@physics.gu.se.
authors.forename: B
authors.initials: B
authors.lastname: Mehlig
mesh_terms: D003710:Demography; D015894:Genome, Human; D006801:Humans; D008962:Models, Theoretical; D020641:Polymorphism, Single Nucleotide
keywords: Bottleneck; Coalescent approximation; Infinite-sites model; Single nucleotide polymorphism; Site frequency spectrum (SFS)