Likelihood-ratio tests for positive selection of human and mouse duplicate genes reveal nonconservative and anomalous properties of widely used methods

Two commonly used methods based on likelihood-ratio tests (LRTs) for detecting positive Darwinian selection at the molecular level were applied to a data set of 604 gene families containing two members in the human genome and two members in the mouse genome. These methods detected positive selection in a very high proportion of families; in over 50% of families, there was significant evidence of positive selection by one or both methods. However, less than a third of families showing evidence for positive selection by at least one of the methods showed evidence of positive selection by both methods. The outcome of these tests was predicted better by sequence length, G + C content at third-codon positions, and the level of synonymous substitution than by the level of nonsynonymous substitution or the ratio of nonsynonymous to synonymous substitution. These results suggested that LRT-based tests for positive selection may be sensitive to certain factors that make it difficult to reconstruct the true pattern of nucleotide substitution.