A quantitative study of the dynamics of adaptive mutation appearance

We present two dynamical models for the appearance of adaptive mutations, w hich permit a quantitative comparison with experimental observations. The m odels quantify two alternative pictures: The hyper-mutating sub-population picture, and the population-wide mutation picture. We find that both models are equally successful in reproducing the results of experiments in which a single mutation is required. They also enable us to estimate the values o f key biological parameters, such as successful mutation rates. We then ana lyze the multiple mutations experiment of Rosche and Foster (Proc. Natl. Ac ad. Sci. 96 (1999) 6862) using a combined model, again obtaining quantitati ve agreement between theory and experiment. We conclude that additional exp erimental tests concentrating on the dynamics of mutation appearance, and e specially the ones involving double mutations, are required in order to det ermine the relative contribution of the two mechanisms to adaptive mutation s appearance. (C) 2001 Elsevier Science B.V. All rights reserved.