Accuracy and Ageing

Abstract

It is taken for granted that present day organisms have a variety of devices to ensure that macromolecules are made accurately and also that, in the case of DNA, structural integrity is maintained by elaborate repair mechanisms. Yet this cannot always have been the case, since primitive organisms must have been far less accurate. Increased accuracy and repair would confer a selective advantage, leading eventually by evolution to the situation we now observe. However, the avoidance or elimination of errors requires the consumption of metabolic energy. This is well known in the case of DNA synthesis, where errors can be removed by a proof-reading exonuclease mechanism, and each wrong nucleoside triphosphate is converted to a monophosphate. The synthesis of repair enzymes is also energy-consuming. Less is known about the mechanisms which ensure accurate protein synthesis, but it is likely that ribosomes and associated factors not only allow the assembly of polypeptide chains, but also effectively discriminate against the incorporation of wrong amino acids, perhaps by a kinetic proof reading mechanism or its equivalent (1,2). Another way of increasing accuracy is to reduce the rate of synthesis of macromolecules, since this allows more time for the dissociation of incorrect substrate-enzyme complexes (3). There is evidence that mutations in ribosomal proteins which increase accuracy also reduce the rate of translation (4). There is also much evidence that when defective proteins are synthesised, they are preferentially degraded (5,6).