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Mol. Biol. Evol. 18(8):15851592. 2001 2001 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038

Summary: 1585
Mol. Biol. Evol. 18(8):1585­1592. 2001
2001 by the Society for Molecular Biology and Evolution. ISSN: 0737-4038
Accuracy and Power of the Likelihood Ratio Test in Detecting Adaptive
Molecular Evolution
Maria Anisimova, Joseph P. Bielawski, and Ziheng Yang
Department of Biology, Galton Laboratory, University College London, London, England
The selective pressure at the protein level is usually measured by the nonsynonymous/synonymous rate ratio (
dN/dS), with 1, 1, and 1 indicating purifying (or negative) selection, neutral evolution, and diversifying
(or positive) selection, respectively. The ratio is commonly calculated as an average over sites. As every functional
protein has some amino acid sites under selective constraints, averaging rates across sites leads to low power to
detect positive selection. Recently developed models of codon substitution allow the ratio to vary among sites
and appear to be powerful in detecting positive selection in empirical data analysis. In this study, we used computer
simulation to investigate the accuracy and power of the likelihood ratio test (LRT) in detecting positive selection
at amino acid sites. The test compares two nested models: one that allows for sites under positive selection (with
1), and another that does not, with the 2 distribution used for significance testing. We found that use of the
2 distribution makes the test conservative, especially when the data contain very short and highly similar sequences.
Nevertheless, the LRT is powerful. Although the power can be low with only 5 or 6 sequences in the data, it was
nearly 100% in data sets of 17 sequences. Sequence length, sequence divergence, and the strength of positive
selection also were found to affect the power of the LRT. The exact distribution assumed for the ratio over sites


Source: Anisimova, Maria - Institute of Scientific Computing, Eidgenössische Technische Hochschule Zürich (ETHZ)
Yang, Ziheng - Department of Genetics, Evolution and Environment, University College London


Collections: Biology and Medicine; Environmental Sciences and Ecology