RELEVANCE OF ADAPTIVE MUTATIONS ARISING IN NONDIVIDING CELLS OF MICROORGANISMS TO AGE-RELATED-CHANGES IN MUTANT PHENOTYPES OF NEURONS

Brattleboro rats do not produce vasopressin (VP) because of a germ-lin e single-base deletion (di) that causes a frame shift downstream from the VP sequences and a loss of a stop codon,The resulting frame-shifte d peptide precursor does not enter the secretory pathway in hypothalam ic neurons, thereby blocking the neurosecretion of VP and other peptid es, Yet, from birth onwards, a subpopulation of neurons in di/di rats slowly accumulates revertant cells with a hemizygous wild-type phenoty pe, Because the rate of reversion during aging is slowed by vasopressi n infusion, it is of interest to consider these phenomena in relation to recent observations on 'adaptive' mutations in single cell bacteria and yeast that enable reversion of mutations that blocked cell divisi on under conditions of nutrient deficits, In considering mechanisms th at could produce revertant phenotypes in non-dividing cells of both pr o-and eukaryotes, we note the pertinence of transcription-coupled repa ir and SOS 'error-prone' repair.