Genome-wide screen for deficiencies modifying Cyclin G -induced developmental instability in Drosophila melanogaster

In spite of long-lasting interest and research efforts, the genetic bases of developmental stability – the robustness to developmental noise – and its most commonly used estimator, fluctuating asymmetry (FA), remain poorly understood. The Drosophila melanogaster Cyclin G gene ( CycG ) encodes a transcriptional cyclin that regulates growth and the cell cycle. Over-expression of a potentially more stable isoform of the protein (deleted of a PEST-rich domain, hereafter called CycG ^ΔP ) induces extreme wing size and shape FA ( i.e . high developmental noise), indicating a major disruption of developmental stability. Previous attempts to identify the genetic bases of FA have been impeded by developmental stability itself, i.e . by the constitutively low level of developmental noise, strongly limiting the power to detect any effect. Here, we leverage the extreme developmental instability induced by the overexpression of CycG ^ΔP , to explore the genetic bases of FA with a considerably enhanced power: we use this genetic context to perform a genome-wide screen for deficiencies that enhance or reduce CycG ^ΔP -induced wing FA. 499 deficiencies uncovering about 90% of the euchromatic genome were combined with a recombinant chromosome expressing CycG ^ΔP . We identified 13 and 16 deficiencies that enhance and decrease FA, respectively. Analysis of mutants for some genes located in these deficiencies shows that Cyclin G ensures homogeneous growth of organs in synergy with the major morphogens of the wing, Dpp and Wg, as well as the Hippo and InR/TOR pathways. They also reveal that CycG ^ΔP -induced FA involves Larp, a potential direct interactor of Cyclin G, that regulates translation at the mitochondrial membrane. This opens up new research perspectives for understanding developmental stability, suggesting a significant role for mitochondrial activity in this process.