Molecular Biology and Evolution, Vol 11, 436-442, Copyright © 1994 by Society for Molecular Biology and Evolution
J Wakeley
Substitution-rate variation among sites and differences in the
probabilities of change among the four nucleotides are conflated in DNA
sequence comparisons. When variation in rate exists among sites but is
ignored, biases in the rates of change among nucleotides are
underestimated. This paper provides a quantification of this effect when
the observed proportions of transitions, P, and transversions, Q, between
two sequences are used to estimate transition bias. The utility of P/Q as
an estimator is examined both with and without rate variation among sites.
A gamma-distributed-rates model is used to illustrate the effect that
variation among sites has on estimates of transition bias, but it is argued
that the basic results should hold for any pattern of rate variation. Naive
estimates of the extent of transition bias, those that ignore rate
variation when it is present, can seriously underestimate its true value.
The extent of this underestimation increases with the amount of rate
variation among sites. An example using human mitochondrial DNA shows that
a simple comparison of the proportions of transitions and transversions in
recently diverged sequences underestimates the level of transition bias by
approximately 15%. This does not depend on the use of P/Q to estimate
transition bias; maximum-likelihood methods give similar results.
ORIGINAL ARTICLE
Substitution-rate variation among sites and the estimation of transition bias
Department of Integrative Biology, University of California, Berkeley 94720.
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