Originally published as Genetics Published Articles Ahead of Print on January 16, 2005.

Genetics, Vol. 169, 1753-1762, March 2005, Copyright © 2005
doi:10.1534/genetics.104.032144

Detecting Amino Acid Sites Under Positive Selection and Purifying Selection

Tim Massingham¹ and Nick Goldman

European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, United Kingdom

¹ Corresponding author: Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SD, United Kingdom.
E-mail: timm{at}ebi.ac.uk

An excess of nonsynonymous over synonymous substitution at individual amino acid sites is an important indicator that positive selection has affected the evolution of a protein between the extant sequences under study and their most recent common ancestor. Several methods exist to detect the presence, and sometimes location, of positively selected sites in alignments of protein-coding sequences. This article describes the "sitewise likelihood-ratio" (SLR) method for detecting nonneutral evolution, a statistical test that can identify sites that are unusually conserved as well as those that are unusually variable. We show that the SLR method can be more powerful than currently published methods for detecting the location of positive selection, especially in difficult cases where the strength of selection is low. The increase in power is achieved while relaxing assumptions about how the strength of selection varies over sites and without elevated rates of false-positive results that have been reported with some other methods. We also show that the SLR method performs well even under circumstances where the results from some previous methods can be misleading.

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