Originally published as Genetics Published Articles Ahead of Print on May 23, 2005.

Genetics, Vol. 170, 1401-1410, July 2005, Copyright © 2005
doi:10.1534/genetics.104.038224

Distinguishing Between Selective Sweeps and Demography Using DNA Polymorphism Data

Jeffrey D. Jensen*, Yuseob Kim{dagger},1, Vanessa Bauer DuMont*, Charles F. Aquadro*,2 and Carlos D. Bustamante{dagger}

* Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York 14853
{dagger} Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853

2 Corresponding author: Department of Molecular Biology and Genetics, 235 Biotechnology Bldg., Cornell University, Ithaca, NY 14850.
E-mail: cfa1{at}cornell.edu

In 2002 Kim and Stephan proposed a promising composite-likelihood method for localizing and estimating the fitness advantage of a recently fixed beneficial mutation. Here, we demonstrate that their composite-likelihood-ratio (CLR) test comparing selective and neutral hypotheses is not robust to undetected population structure or a recent bottleneck, with some parameter combinations resulting in a false positive rate of nearly 90%. We also propose a goodness-of-fit test for discriminating rejections due to directional selection (true positive) from those due to population and demographic forces (false positives) and demonstrate that the new method has high sensitivity to differentiate the two classes of rejections.




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