Induction of mutations in Drosophila melanogaster gypsy retroelements by modulation of intracellular deoxynucleoside triphosphate pools in vivo.
The retroviral mutation rate is susceptible to a number of variables, including the balance between intracellular deoxynucleoside triphosphate (dNTP) pools. While this follows from tissue culture studies, the issue has never been addressed directly in vivo. To explore this question in a tractable experimental system, we analyzed the impact of thymidine treatment on the synthesis of gypsy retroelement cDNA from Drosophila melanogaster during development through to hatching. The mutation frequency was enhanced approximately 16-fold over the levels seen in the experimental background. Due to the lack of proofreading, these gypsy elements represent hypervariable loci within the Drosophila genome, suggesting that dNTP pool imbalances in vivo are mutagenic.
Terzian
Christophe
C
Unité de Rétrovirologie Moléculaire, CNRS URA 3015, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex 15, France.
Henry
Michel
M
Meyerhans
Andreas
A
Wain-Hobson
Simon
S
Vartanian
Jean-Pierre
JP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D004331:Drosophila melanogaster / Q000235:genetics* / Q000254:growth & development; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D008969:Molecular Sequence Data; D016296:Mutagenesis / Q000187:drug effects*; D010063:Ovum / Q000187:drug effects; D018626:Retroelements / Q000235:genetics*; D013936:Thymidine / Q000633:toxicity*
D003062:Codon; D018626:Retroelements; D013936:Thymidine