Fixed genetic instability in Neurospora crassa.

NE of the most convincingly documented genetic phenomena is the great Ovariabi l i t y in spontaneous mutation frequencies at different genetic sites. This variability is seen most readily in BENZER’S topographic maps of the rII region of phage T4 in which the linear distributions of mutants of different origins are compared (BENZER 1961). Restricting our attention to spontaneously arising mutants, it is clear that certain sites (or nucleotide base pairs in the DNA molecule) are much more susceptible to the mechanism(s) of spontaneous mutation than others, and these sites have been designated as “hot spots.” Thus the term “hot spot” denotes comparative instability. Closely analogous is the case of autonomous instability in mutant alleles. These have been described in a variety of organisms (DEMEREC 1941; LEDERBERG 1952; SCHWARTZ 1960) and it appears that their instability reflects an allelespecific, inherent high probability of mutation to a more stable state that is independent of extrinsic factors. Many cases of instability undoubtedly reflect chromosomal breakage phenomena, and others an instability due to activators (RHOADES 1941) or mutator genes (DEMEREC 1941; SKAAR 1956); however, it appears highly probable that many other unstable alleles arising after exposure to various base analogues or chemical mutagens represent authentic transitional mutations (i.e., substitutions of the purine-for-purine, pyrimidine-for-pyridimide type) (FREESE 1959) which are unstable. This paper reports an analysis of instability in which a genetic site has mutated to a state of permanent high spontaneous mutability in either of two allelic (and phenotypically different) forms.