By comparing published and experimental data on spontaneous mutability of early genes controlling biosynthesis of purine nucleotides (BPN) in different yeast species in the system “from red to white,” it was shown that the PUR4 gene encoding 5"-phosphoribosylformyl glycinamidine synthetase (FGAM-synthetase) (EC 6.3.5.3) is the most mutable gene in yeastSaccharomyces cerevisiae (the ADE6 gene), Schizosaccharomyces pombe(the ade3 gene), andPichia methanolica (theADE5 gene). This correlates with a considerably large size of the FGAM-synthetase polypeptide, as compared to the products of other genes belonging to this group. Study of characteristics of spontaneous mutations in early BPN genes of P. methanolica demonstrated that the vast majority of unstable ade5sU alleles (mutations with a high reversion frequency ranging from 0.2 × 10–6 to 2 × 10–6) appeared solely among mutants for the ADE5 gene. Based on these results, it was assumed that there are two independent mechanisms responsible for reversions of spontaneous mutations in this gene. The DNA sequence that can compensate for theP. methanolica ade5mutation and probably is the structural P-ADE5gene, was cloned from a genomic library of P. methanolicaby the ade6 mutation complementation in the recipient S. cerevisiae strain.