SPONTANEOUS MUTATIONS IN MAMMALIAN-CELLS

Spontaneous or background mutation in mammals plays an important role in both medical and evolutionary contexts. However, establishing mutat ion frequencies or rates has not always been easy. When the field of m ammalian mutagenesis was in its infancy, the word ''variant'' rather t han ''mutant'' was often used because the genetic nature of the observ ed phenotypic alterations could not be adequately proven. Nowadays num erous target genes have been identified in which mutant frequencies ca n be measured, and occasionally even rates can be estimated. Indeed, t he genetic basis for 'variants' now often comes from direct DNA sequen cing. This review describes the most often used and best understood ge netic markers for mutation research and examines their usefulness. In addition, mutational specificity is compared for several loci and the use of DNA-sequence data in determining the origins of spontaneous mut ation is also discussed. An important observation is that spontaneous mutation frequencies of similarly sized genes can vary by more than an order of magnitude. Chromosomal location, the nature of the gene prod uct and mutational specificity may offer a partial explanation.