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Originally published as Genetics Published Articles Ahead of Print on May 6, 2005.
Genetics, Vol. 170, 1411-1421, July 2005, Copyright © 2005
doi:10.1534/genetics.104.035097
A Composite-Likelihood Approach for Detecting Directional Selection From DNA Sequence Data
Lan Zhu and Carlos D. Bustamante1
Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853
1 Corresponding author: Department of Biological Statistics and Computational Biology, 101 Biotechnology Bldg., Cornell University, Ithaca, NY 14853.
E-mail: cdb28{at}cornell.edu
We present a novel composite-likelihood-ratio test (CLRT) for detecting genes and genomic regions that are subject to recurrent natural selection (either positive or negative). The method uses the likelihood functions of HARTL et al. (1994) for inference in a Wright-Fisher genic selection model and corrects for nonindependence among sites by application of coalescent simulations with recombination. Here, we (1) characterize the distribution of the CLRT statistic (
) as a function of the population recombination rate (R = 4Ner); (2) explore the effects of bias in estimation of R on the size (type I error) of the CLRT; (3) explore the robustness of the model to population growth, bottlenecks, and migration; (4) explore the power of the CLRT under varying levels of mutation, selection, and recombination; (5) explore the discriminatory power of the test in distinguishing negative selection from population growth; and (6) evaluate the performance of maximum composite-likelihood estimation (MCLE) of the selection coefficient. We find that the test has excellent power to detect weak negative selection and moderate power to detect positive selection. Moreover, the test is quite robust to bias in the estimate of local recombination rate, but not to certain demographic scenarios such as population growth or a recent bottleneck. Last, we demonstrate that the MCLE of the selection parameter has little bias for weak negative selection and has downward bias for positively selected mutations.
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