Molecular Biology and Evolution, Vol 16, 1068-1078, Copyright © 1999 by Society for Molecular Biology and Evolution
NJ Tourasse and WH Li
Relative-rate tests have previously been developed to compare the
substitution rates of two sequences or two groups of sequences. These tests
usually assume that the process of nucleotide substitution is stationary
and the same for all lineages, i.e., uniform. In this study, we conducted
simulations to assess the performance of the relative-rate tests when the
molecular-clock (MC) hypothesis is true (i.e., there is no rate difference
between lineages), but the stationarity and uniformity assumptions are
violated. Kimura's and bias-corrected LogDet distances were used. We found
that the computation of the variances and covariances of LogDet distances
had to be modified, because the constraint that the sum of the frequencies
of the 16 nucleotide pair types is equal to 1 must be imposed. Comparison
of the rates of two single sequences (Wu and Li's test) or two groups of
sequences (Li and Bousquet's test) gave similar results. When the sequences
are long (> or = 500 nt), the test based on LogDet distances and their
appropriate variances and covariances is appropriate even when the
substitution process is not stationary and/or not uniform. That is, at the
5% significance level, the test rejects the MC hypothesis in about 5% of
the simulation replicates. In contrast, if the sequences are short (< or
= 200 bases) and highly divergent, the LogDet test is very conservative due
to overestimation of the variances of the distances. When the uniformity
assumption is violated, the relative-rate test based on Kimura's distances
can be severely misleading because of differences in base composition
between sequences. However, if the uniformity assumption held and so the
base frequencies remained similar among sequences, the rate of rejection
turned out to be close to 5%, especially with short sequences. Under such
conditions, the test using Kimura's distances performs better than the
LogDet test. The reason seems to be that these distances are less affected
by a reduction in the number of sites than the LogDet distances because
they depend on only two parameters.
ORIGINAL ARTICLE
Performance of the relative-rate test under nonstationary models of nucleotide substitution
Department of Ecology and Evolution, University of Chicago, Illinois 60637, USA.
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