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      Statistical Tests for Detecting Positive Selection by Utilizing High-Frequency Variants

      , , ,
      Genetics
      Genetics Society of America

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          Abstract

          By comparing the low-, intermediate-, and high-frequency parts of the frequency spectrum, we gain information on the evolutionary forces that influence the pattern of polymorphism in population samples. We emphasize the high-frequency variants on which positive selection and negative (background) selection exhibit different effects. We propose a new estimator of theta (the product of effective population size and neutral mutation rate), thetaL, which is sensitive to the changes in high-frequency variants. The new thetaL allows us to revise Fay and Wu's H-test by normalization. To complement the existing statistics (the H-test and Tajima's D-test), we propose a new test, E, which relies on the difference between thetaL and Watterson's thetaW. We show that this test is most powerful in detecting the recovery phase after the loss of genetic diversity, which includes the postselective sweep phase. The sensitivities of these tests to (or robustness against) background selection and demographic changes are also considered. Overall, D and H in combination can be most effective in detecting positive selection while being insensitive to other perturbations. We thus propose a joint test, referred to as the DH test. Simulations indicate that DH is indeed sensitive primarily to directional selection and no other driving forces.

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          The hitch-hiking effect of a favourable gene

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            The cost of inbreeding in Arabidopsis.

            Population geneticists have long sought to estimate the distribution of selection intensities among genes of diverse function across the genome. Only recently have DNA sequencing and analytical techniques converged to make this possible. Important advances have come from comparing genetic variation within species (polymorphism) with fixed differences between species (divergence). These approaches have been used to examine individual genes for evidence of selection. Here we use the fact that the time since species divergence allows combination of data across genes. In a comparison of amino-acid replacements among species of the mustard weed Arabidopsis with those among species of the fruitfly Drosophila, we find evidence for predominantly beneficial gene substitutions in Drosophila but predominantly detrimental substitutions in Arabidopsis. We attribute this difference to the Arabidopsis mating system of partial self-fertilization, which corroborates a prediction of population genetics theory that species with a high frequency of inbreeding are less efficient in eliminating deleterious mutations owing to their reduced effective population size.
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              The effect of strongly selected substitutions on neutral polymorphism: Analytical results based on diffusion theory

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                Author and article information

                Journal
                Genetics
                Genetics
                Genetics Society of America
                0016-6731
                1943-2631
                November 22 2006
                November 2006
                November 2006
                September 01 2006
                : 174
                : 3
                : 1431-1439
                Article
                10.1534/genetics.106.061432
                1667063
                16951063
                47469753-b08f-401c-b59a-73ab45435864
                © 2006
                History

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