Mediation of Drosophila autosomal dosage effects and compensation by network interactions
- Equal contributors
1 Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, 50 South Drive, Bethesda, MD 20892, USA
2 Department of Biology, Florida State University, 319 Stadium Drive, Tallahassee, FL 32306, USA
3 Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20814, USA
4 Department of Biology, 385 Serra Mall, Stanford University, Stanford, CA 94304, USA
5 Human Genome Sequencing Center, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, USA
6 Genomics Core, National Institute of Diabetes and Digestive and Kidney Diseases, 8 Center Drive, Bethesda, MD 20814, USA
7 Biochemical Science Division, Molecular Measurement Laboratory, National Institute of Standards and Technology, 100 Bureau Drive, Gaithersburg, MD 20899, USA
8 Department of Biology, Indiana University, 1001 East 3rd Street, Bloomington, IN 47405, USA
Genome Biology 2012, 13:R28 doi:10.1186/gb-2012-13-4-r28Published: 24 April 2012
Gene dosage change is a mild perturbation that is a valuable tool for pathway reconstruction in Drosophila. While it is often assumed that reducing gene dose by half leads to two-fold less expression, there is partial autosomal dosage compensation in Drosophila, which may be mediated by feedback or buffering in expression networks.
We profiled expression in engineered flies where gene dose was reduced from two to one. While expression of most one-dose genes was reduced, the gene-specific dose responses were heterogeneous. Expression of two-dose genes that are first-degree neighbors of one-dose genes in novel network models also changed, and the directionality of change depended on the response of one-dose genes.
Our data indicate that expression perturbation propagates in network space. Autosomal compensation, or the lack thereof, is a gene-specific response, largely mediated by interactions with the rest of the transcriptome.