OST structural gene mutations, which are not of the "nonsense" or "frame-Mshift" type, are recognized solely by effects on some property of the corresponding gene product or enzyme. A number of these mutations in a gene of the L-arabinose operon in Escherichia co2i have also been found (ENGLESBERG 1961 ) to alter the rate of synthesis of the enzyme as well. This form of dual biochemical effect could be distinguished from effects on enzyme synthesis determined by nonsense" or "frameshift"

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... ns (NEWTON, BECKWITH, ZIPSER and BRENNER 1965; MARTIN, SILBERT, SMITH and WHITFIELD 1966; and YANOFSKY and ITO 1966) in that the gene product, although inactive was still made (CRM+) and the normal coordinate relationship in the synthesis of all three enzymes in the operon was usually maintained, i.e. there was no polarity (LEE and ENGLES-BERG 1963). Moreover, these mutations sometimes determined a coordinate increase as well as decrease in the rate of enzyme synthesis. It was suggested (LEE and ENGLESBERG 1963) that the inability to demonstrate this form of dualeffect in other systems might be related to individual biochemical properties peculiar to each. Evidence for a similar effect of mutation in the dihydrofolate reductase gene of Diplococcus pneumoniae is reported now. Of interest was the fact that these mutations, unlike those found in the L-arabinose operon of E. coEi, determined only increased rates of enzyme synthesis and at the same time had no grossly adverse effect on catalytic properties. Mutant strains of D. pneumoniae with elevated levels of dihydrofolate reductase can be isolated by selecting for resistance to the antifolate, amethopterin. These effects on enzyme synthesis occur exclusively as a result of mutation in the previously identified A M E I locus ( SIROTNAK, LUNT and HUTCHISON 1964) . The current studies revealed that almost all of these mutations are within the structural gene for the enzyme itself. Certain genetic properties and biochemical effects of a few of these mutations have been described earlier (SIROTNAK, LUNT