INCREASED ACCURACY IN ANALYTICAL MOLECULAR DISTANCE ESTIMATION

Analytical molecular distance estimates can be inaccurate and biased e stimates of the total number of substitutions not only when the model of evolution they are based on is incorrect, but also when the method of estimating the total is too simple. This comes about because when t here are different types of substitutions occurring simultaneously, it can become extremely difficult to estimate the number of the more qui ckly evolving type, and the variance of this larger number can overwhe lm the total estimate. In this paper, in an extension of earlier work with a simple two-parameter model of evolution, more accurate analytic al distances are derived for models appropriate to a variety of known DNA types using generalized least squares principles of noise reductio n. It is shown that the new estimates can be applied to achieve more a ccurate results for site-to-site rate variation, regions with biased n ucleotide frequencies, and synonymous sites in protein-coding regions. This study also includes a methodology to obtain accurate distance es timates for large numbers of sequence regions evolving in different ma nners. (C) 1998 Academic Press.