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Induction of Mutations in Drosophila melanogaster gypsy Retroelements by Modulation of Intracellular Deoxynucleoside Triphosphate Pools In Vivo

Christophe Terzian,^1, Michel Henry,² Andreas Meyerhans,³ Simon Wain-Hobson,² and Jean-Pierre Vartanian^2*

Institut de Génétique Humaine—CNRS, 141, rue de la Cardonille, F-34396 Montpellier Cedex 5, France,¹ Unité de Rétrovirologie Moléculaire, CNRS URA 3015, Institut Pasteur, 28 rue du Dr. Roux, F-75724 Paris cedex 15, France,² Department of Virology, Institute of Medical Microbiology, University of the Saarland, D-66421 Homburg/Saar, Saarbrücken, Germany³

Received 20 November 2006/ Accepted 5 February 2007

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.

Published ahead of print on 14 February 2007.

Present address: EPHE, UMR754-Université Lyon 1, 50 avenue Tony Garnier, F69366 Lyon Cedex 07, France.