Wakeley J
Department of Integrative Biology, University of California, Berkeley 94720.
Mol Biol Evol. 1994 May;11(3):436-42. doi: 10.1093/oxfordjournals.molbev.a040124.
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.
在DNA序列比较中，位点间的替换率变化以及四种核苷酸之间变化概率的差异相互交织。当位点间存在速率变化却被忽略时，核苷酸间变化速率的偏差就会被低估。本文在利用两条序列之间观察到的转换比例P和颠换比例Q来估计转换偏差时，对这种效应进行了量化。在考虑和不考虑位点间速率变化的情况下，均考察了P/Q作为估计量的效用。使用伽马分布速率模型来说明位点间变化对转换偏差估计的影响，但有人认为，基本结果对于任何速率变化模式都应成立。对转换偏差程度的简单估计，即在存在速率变化时忽略它的估计，可能会严重低估其真实值。这种低估的程度随着位点间速率变化量的增加而增大。一个使用人类线粒体DNA的例子表明，对近期分化序列中转换和颠换比例进行简单比较，会使转换偏差水平被低估约15%。这并不取决于使用P/Q来估计转换偏差；最大似然法也会给出类似结果。
