Mutants of with increased sensitivity to canavanine were derived from wild-type, -3 (presumably defective in carbamoyl-phosphate synthase for pyrimidine synthesis), (blocked in steps prior to arginine formation) and (blocked in steps prior to glutamate semialdehyde formation) strains, and were classified into eight distinct groups by genetic mapping. Four canavanine-sensitive genes () were allelic or very tightly linked to known loci. The pairs of genes involved were and (arginine requirer), and ) was mapped in linkage group III.

A relationship was shown between the level of intracellular arginine and the extent of canavanine sensitivity; strains contain less intracellular arginine than the less sensitive wild-type. In most cases, this was shown to result from mutations affecting the enzyme(s) involved in arginine metabolism. and were thought to be affected in arginine- and ornithine-synthesizing enzymes, respectively. and exhibited a requirement for citrulline when the two genes were combined and were suggested to be loci specifying the two polypeptide chains of carbamoyl-phosphate synthase for arginine synthesis. was the locus controlling ornithine carbamoyltransferase. The metabolic lesions of the other mutants (, and ) were unclear.

Of the eight mutants, six could suppress and/or mutations: was able to suppress ; and were effective in suppressing ; suppressed both and The mechanism of the and suppressions was explained on the basis of metabolic cross-feeding.


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