Vestigial mutants of Drosophila melanogaster live better in the presence of aminopterin: increased level of dihydrofolate reductase in a mutant.
Vestigial (vg) mutants of Drosophila melanogaster are characterized by atrophied wings. In this paper we show that: (1) aminopterin an inhibitor of dihydrofolate reductase (DHFR) and fluorodeoxyuridine (FUdR), an inhibitor of thymidylate synthetase induce nicks in the wings of wild-type flies and phenocopies of the vg mutant phenotype when vg/+ and vgB/+ flies are reared on these substances (vgB is a deficiency of the vg locus). Only thymidine and thymidylate can rescue the flies from the effect of aminopterin. We propose that the vg phenotype is due to a decrease in the dTMP pool in the wings. (2) Mutant vg strains yield more offspring on medium containing aminopterin than on normal medium. The resistance of vg larvae to the inhibitor seems specific to the gene. This is the first case of aminopterin resistance in living eucaryotes. In contrast sensitivity of the vg larvae to FUdR is observed. (3) An increase in the activity and amount of DHFR is observed in mutant strains as compared with the wild-type flies. Our data suggest that the vg+ gene is a regulatory gene acting on the DHFR gene or a structural gene involved in the same metabolic pathway.
Silber
J
J
Laboratoire de Génétique Quantitative et Moléculaire, Université Paris 7, France.
Bazin
C
C
Le Menn
A
A
D000630:Aminopterin / Q000494:pharmacology*; D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D005467:Floxuridine / Q000494:pharmacology; D008727:Methotrexate / Q000378:metabolism; D010641:Phenotype; D011685:Purine Nucleotides / Q000378:metabolism; D011742:Pyrimidine Nucleotides / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism*; D013940:Thymidylate Synthase / Q000378:metabolism
D011685:Purine Nucleotides; D011742:Pyrimidine Nucleotides; D005467:Floxuridine; D013762:Tetrahydrofolate Dehydrogenase; D013940:Thymidylate Synthase; D000630:Aminopterin; D008727:Methotrexate