Zeng K, Fu YX, Shi SH, Wu CI.. Statistical tests for detecting positive selection by utilizing high-frequency variants. Genetics 174: 1431-1439

State Key Laboratory of Biocontrol, Ministry of Education, Sun Yat-sen University, Guangzhou, China.
Genetics (Impact Factor: 5.96). 12/2006; 174(3):1431-9. DOI: 10.1534/genetics.106.061432
Source: PubMed


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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Available from: Suhua Shi, Jun 03, 2015
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    • "It also results in "structured" genealogies in which the means and variances of coalescence times (e.g., time to the most recent common ancestor) are large, resulting in an excess of intermediate frequency variants in the SFS (Wakeley 1999). Balancing selection leads to a similar structure, and to an excess of variants at intermediate frequency (Tajima 1989; Fay and Wu 2000; Barton and Etheridge 2004; Zeng et al. 2006). Directional selection leads to genealogies with both star shapes (leading to the common ancestor of the selected lineages) and long branches (due to remaining ancestral lineages and/or recombination with the selected haplotype), and generates an excess of variants at both low and high frequency (Barton 1998). "
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    • "Nucleotide diversity over whole gene regions was measured as p (Nei and Li 1979) and y W (Watterson 1975). DH (Fay and Wu 2000; Zeng et al. 2006) was also calculated in 5 kb sliding windows moving with a step of 500 bp. Sliding window analyses have an inherent multiple testing problem that is difficult to correct because of the nonindependence of windows. "
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