Mediation of Drosophila autosomal dosage effects and compensation by network interactions

John H. Malone, Dong Yeon Cho, Nicolas R. Mattiuzzo, Carlo G. Artieri, Lichun Jiang, Ryan K. Dale, Harold E. Smith, Jennifer McDaniel, Sarah Munro, Marc Salit, Justen Andrews, Teresa M. Przytycka, Brian Oliver

Research output: Contribution to journalArticlepeer-review

72 Scopus citations

Abstract

Background: 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.Results: 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 expression, and the directionality of change depended on the response of one-dose genes.Conclusions: 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.

Original languageEnglish (US)
Article numberr28
JournalGenome biology
Volume13
Issue number4
DOIs
StatePublished - Apr 24 2012
Externally publishedYes

Bibliographical note

Funding Information:
We thank the Drosophila Stock Center (Bloomington, IN, USA) and Steve Russell (Cambridge, UK) for flies and the Spyros Artavanis-Tsakonas lab (Boston, MA, USA) for sharing pre-publication protein-protein interaction data. We thank fellow members of our labs for stimulating discussion, advice, feedback, and encouragement. This research was supported by the Intramural Research Programs of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Library of Medicine (NLM), and National Institute of Standards and Technology (NIST). Certain commercial equipment, instruments, or materials are identified in this document. Such identification does not imply recommendation or endorsement by NIH or NIST, nor does it imply that the products identified are necessarily the best available for the purpose.

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