302 CELL HEREDITY 



furthermore, were shown to be nonalleMc and, therefore, not repeats of 

 the same mutation. The temperature-sensitive mutants of Horowitz were 

 not checked for allehsm. 



Roth methods proxide estimates of irreparahiHtv, and both involve 

 techniques and assumptions which are open to criticism. The impressive 

 finding, however, is not the discrepancy between 50 per cent in one ex- 

 periment and 90 per cent in the other, but rather the agreement between 

 the methods in demonstrating that the majoritv of nmtations, spon- 

 taneous and UV-induced, arising in Neurospora have never been studied, 

 and mav represent a reser\oir of unknown gene functions. 



These findings are very much in hne with the results of classical muta- 

 tion rate studies in Drosophila, in which the frequencies of lethal and 

 of visible mutations were compared. The quantitative measure of mu- 

 tation in Drosophila began with MuUer's invention of the ClB method 

 for counting the numbers of recessive lethals on the X chromosome. 

 This and another method, using attached-X stocks, can also be employed 

 for estimating the frequency of visible mutations. In comparative 

 studies, the frequency of lethals was found to be about double that of 

 visible mutations, following X-radiation. The spontaneous frequencies 

 are too low to be studied by these methods. 



It should be quite clear that the nature of "lethals" in Drosophila may 

 have nothing more in common with the 'irreparables ' in Neurospora 

 than that both represent unknown gene functions, accounting for the 

 majority of detected mutations. In considering gene functions in an 

 animal like Drosophila, one must take into account the complexities of 

 embrvological differentiation and the mechanisms required for integra- 

 tion of organs and tissues. We are hard put even to identify gene func- 

 tions at the cellular level. There at least one may make a beginning and 

 set up hypotheses susceptible to test. 



Some suggestions have been made concerning the nature of "irrep- 

 arable" mutations in Neurospora. For example, some may represent 

 effects upon enzvmes which catalyze reactions of very labile substrates or 

 complexes which cannot be supplied readily from the medium. Other 

 mutations may alter permeability; one such mutant in Neurospora, 

 called osmotic, cannot tolerate media of high osmolarity. Some mu- 

 tations may be lethal because precursors accumulate behind the blocked 

 reaction and interfere directly or indirectly with growth. Clearly, 

 with a little ingenuity, one may compile long lists of possible modes 

 of lethality at the cellular level; for many of them there are examples 

 on record. 



These suggestions all refer to mutant effects depending ultimately upon 

 the cell's ability to synthesize a particular enzyme. Is there evidence 



