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      Evaluating the Use of ABBA–BABA Statistics to Locate Introgressed Loci

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          Abstract

          Several methods have been proposed to test for introgression across genomes. One method tests for a genome-wide excess of shared derived alleles between taxa using Patterson’s D statistic, but does not establish which loci show such an excess or whether the excess is due to introgression or ancestral population structure. Several recent studies have extended the use of D by applying the statistic to small genomic regions, rather than genome-wide. Here, we use simulations and whole-genome data from Heliconius butterflies to investigate the behavior of D in small genomic regions. We find that D is unreliable in this situation as it gives inflated values when effective population size is low, causing D outliers to cluster in genomic regions of reduced diversity. As an alternative, we propose a related statistic f ^ d , a modified version of a statistic originally developed to estimate the genome-wide fraction of admixture. f ^ d is not subject to the same biases as D, and is better at identifying introgressed loci. Finally, we show that both D and f ^ d outliers tend to cluster in regions of low absolute divergence ( d XY ), which can confound a recently proposed test for differentiating introgression from shared ancestral variation at individual loci.

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          Most cited references30

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          Hybridization and speciation.

          Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near-instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky-Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock-on effects on speciation both within and outside regions of hybridization. © 2013 The Authors. Journal of Evolutionary Biology © 2013 European Society For Evolutionary Biology.
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            Testing for ancient admixture between closely related populations.

            One enduring question in evolutionary biology is the extent of archaic admixture in the genomes of present-day populations. In this paper, we present a test for ancient admixture that exploits the asymmetry in the frequencies of the two nonconcordant gene trees in a three-population tree. This test was first applied to detect interbreeding between Neandertals and modern humans. We derive the analytic expectation of a test statistic, called the D statistic, which is sensitive to asymmetry under alternative demographic scenarios. We show that the D statistic is insensitive to some demographic assumptions such as ancestral population sizes and requires only the assumption that the ancestral populations were randomly mating. An important aspect of D statistics is that they can be used to detect archaic admixture even when no archaic sample is available. We explore the effect of sequencing error on the false-positive rate of the test for admixture, and we show how to estimate the proportion of archaic ancestry in the genomes of present-day populations. We also investigate a model of subdivision in ancestral populations that can result in D statistics that indicate recent admixture.
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              The landscape of Neandertal ancestry in present-day humans

              Analyses of Neandertal genomes have revealed that Neandertals have contributed genetic variants to modern humans 1–2 . The antiquity of Neandertal gene flow into modern humans means that regions that derive from Neandertals in any one human today are usually less than a hundred kilobases in size. However, Neandertal haplotypes are also distinctive enough that several studies have been able to detect Neandertal ancestry at specific loci 1,3–8 . Here, we have systematically inferred Neandertal haplotypes in the genomes of 1,004 present-day humans 12 . Regions that harbor a high frequency of Neandertal alleles in modern humans are enriched for genes affecting keratin filaments suggesting that Neandertal alleles may have helped modern humans adapt to non-African environments. Neandertal alleles also continue to shape human biology, as we identify multiple Neandertal-derived alleles that confer risk for disease. We also identify regions of millions of base pairs that are nearly devoid of Neandertal ancestry and enriched in genes, implying selection to remove genetic material derived from Neandertals. Neandertal ancestry is significantly reduced in genes specifically expressed in testis, and there is an approximately 5-fold reduction of Neandertal ancestry on chromosome X, which is known to harbor a disproportionate fraction of male hybrid sterility genes 20–22 . These results suggest that part of the reduction in Neandertal ancestry near genes is due to Neandertal alleles that reduced fertility in males when moved to a modern human genetic background.
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                Author and article information

                Journal
                Mol Biol Evol
                Mol. Biol. Evol
                molbev
                molbiolevol
                Molecular Biology and Evolution
                Oxford University Press
                0737-4038
                1537-1719
                January 2015
                22 September 2014
                22 September 2014
                : 32
                : 1
                : 244-257
                Affiliations
                1Department of Zoology, University of Cambridge, Cambridge, United Kingdom
                Author notes
                *Corresponding author: E-mail: shm45@ 123456cam.ac.uk .

                Associate editor: Doris Bachtrog

                Article
                msu269
                10.1093/molbev/msu269
                4271521
                25246699
                c69dd46d-1c5c-46eb-93df-353b27e8fff4
                © The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Page count
                Pages: 14
                Categories
                Methods

                Molecular biology
                abba–baba,gene flow,introgression,population structure,heliconius,simulation
                Molecular biology
                abba–baba, gene flow, introgression, population structure, heliconius, simulation

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