Kinetics of rapid RNA evolution in vitro.

A rapidly acquired partial resistance to the replicase antagonist, ethidium bromide (EB), seen by Spiegelman and coresearchers in Q beta RNA variants competitively replicating under defined conditions in vitro, reflected existence of a pool of mutant RNA molecules, preadapted to EB, and their cross-propagation from the pre-EB optimum species, MDV-1, and from other kindred variants, some of which remained undetected, according to this quantitative analysis of midivariant RNA replication kinetics. DNAlike features of their evolution, such as the cloning of variants from an MDV-1 subtype and a compliance with the fundamental theorem of natural selection, resulted from the suppression, both real and apparent, of intrinsic RNA heterogeneity through sampling and detection methods, and also by the ascendency of self-propagation over cross-propagation with advancement of a superior variant. The deficit in mean polymer fitness, compared with optimum levels, determines the lower limit of this heterogeneity. Stability conditions for frequency equilibrium and strategies for counteracting viral drug resistance have been considered.