Molecular Biology and Evolution, Vol 15, 568-573, Copyright © 1998 by Society for Molecular Biology and Evolution
Z Yang
An excess of nonsynonymous substitutions over synonymous ones is an
important indicator of positive selection at the molecular level. A lineage
that underwent Darwinian selection may have a nonsynonymous/synonymous rate
ratio (dN/dS) that is different from those of other lineages or greater
than one. In this paper, several codon-based likelihood models that allow
for variable dN/dS ratios among lineages were developed. They were then
used to construct likelihood ratio tests to examine whether the dN/dS ratio
is variable among evolutionary lineages, whether the ratio for a few
lineages of interest is different from the background ratio for other
lineages in the phylogeny, and whether the dN/dS ratio for the lineages of
interest is greater than one. The tests were applied to the lysozyme genes
of 24 primate species. The dN/dS ratios were found to differ significantly
among lineages, indicating that the evolution of primate lysozymes is
episodic, which is incompatible with the neutral theory. Maximum-
likelihood estimates of parameters suggested that about nine nonsynonymous
and zero synonymous nucleotide substitutions occurred in the lineage
leading to hominoids, and the dN/dS ratio for that lineage is significantly
greater than one. The corresponding estimates for the lineage ancestral to
colobine monkeys were nine and one, and the dN/dS ratio for the lineage is
not significantly greater than one, although it is significantly higher
than the background ratio. The likelihood analysis thus confirmed most, but
not all, conclusions Messier and Stewart reached using reconstructed
ancestral sequences to estimate synonymous and nonsynonymous rates for
different lineages.
ORIGINAL ARTICLE
Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution
Department of Biology, University College, London, United Kingdom. z.yang@ucl.ac.uk
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