Bioorganic Chemistry

Phosphate groups are found and used widely in biological chemistry. We have asked whether phosphate groups are likely to be important to the functioning of genetic molecules, including DNA and RNA. From observations made on synthetic analogs of DNA and RNA where the phosphates are replaced by nonanionic linking groups, we infer a set of rules that highlight the importance of the phosphodiester backbone for the proper functioning of DNA as a genetic molecule. The polyanionic backbone appears to give DNA the capability of replication following simple rules, and evolving. The polyanionic nature of the backbone appears to be critical to prevent the single strands from folding, permitting them to act as templates, guiding the interaction between two strands to form a duplex in a way that permits simple rules to guide the molecular recognition event, and buffering the sensitivity of its physicochemical properties to changes in sequence. We argue that the feature of a polyelectrolyte (polyanion or polycation) may be required for a “self-sustaining chemical system capable of Darwinian evolution.” The polyelectrolyte structure therefore may be a universal signature of life, regardless of its genesis, and unique to living forms as well. q 2002 Elsevier Science (USA)