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.
Breivik
Jarle
J
Section for Immunotherapy, University of Oslo at the Norwegian Radium Hospital, 0310 Oslo, Norway. jbreivik@medisin.uio.no
Gaudernack
Gustav
G
D000818:Animals; D003362:Cost-Benefit Analysis; D004249:DNA Damage; D004260:DNA Repair; D001330:Electronic Data Processing; D004777:Environment; D019143:Evolution, Molecular; D042822:Genomic Instability; D006801:Humans; D008433:Mathematics; D008957:Models, Genetic; D009154:Mutation