COMPENSATORY NEARLY NEUTRAL MUTATIONS - SELECTION WITHOUT ADAPTATION

One implication of Kacser's analysis of complex metabolic systems is t hat mutations with small effects exist as a consequence of the typical ly small flux control coefficient relating enzyme activity to the rate of a metabolic process. Although a slightly detrimental mutation is s omewhat less likely to become fixed by chance than a slightly favorabl e mutation, mutations that are slightly detrimental might be expected to be more numerous than favorable mutations owing to the previous inc orporation of favorable mutations by a long history of natural selecti on. The result is that, as Ohta has pointed out, a significant fractio n of mutations that are fixed in evolution are slightly detrimental. I n the long run, the fixation of detrimental mutations in a gene increa ses the opportunity for the occurrence of a compensatory favorable mut ation, either in the same gene or in an interacting gene. On a suitabl y long timescale, therefore, every gene incorporates favorable mutatio ns that compensate for detrimental mutations previously fixed. This fo rm of evolution is driven primarily by natural selection, but it resul ts in no change or permanent improvement in enzymatic function. (C) 19 96 Academic Press Limited