Resolving the evolutionary paradox of genetic instability: a cost-benefit analysis of DNA repair in changing environments

Loss of genetic stability is a critical phenomenon in cancer and antibiotic resistance, and the prevailing dogma is that unstable cells survive because instability provides adaptive mutations. Challenging this view, we have argued that genetic instability arises because DNA repair may be a counterproductive strategy in mutagenic environments. This paradoxical relationship has also been confirmed by explicit experiments, but the underlying evolutionary principles remain controversial. This paper aims to clarify the issue, and presents a model that explains genetic instability from the basic perspective of molecular evolution and information processing. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.