Mediation of Drosophila autosomal dosage effects and compensation by network interactions.

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

doi:10.1186/gb-2012-13-4-r28

Abstract

BackgroundGene 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.ResultsWe 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.ConclusionsOur 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.

Highlights

Gene dosage change is a mild perturbation that is a valuable tool for pathway reconstruction in Drosophila
This suggests that gene dose changes have small additive effects on viability in Drosophila, which may be analogous to the situation in humans, where small regions of segmental aneuploidy are associated with subtle adult phenotyes and large departures from ploidy result in fetal death [3,4,5]
The Drosophila deletion collection (DrosDel) collection offered a key experimental advantage, as all strains are from the same original stock, minimizing genetic background outside of the engineered deletion

Summary

Introduction

Systematic evaluation of gene dose in segmental aneuploids shows that dose changes in the majority of the Drosophila genome are compatible with life [1,2], but if there are enough changes in dose, regardless of the particular genes, viability is greatly reduced [2]. In whole Drosophila showing aneuploidy, some genes in trisomic regions show compensation, while others do not, at both the transcript and protein levels [11,12] All these data indicate that gene dose responses are not always a simple reflection of copy number. We do not have well-developed models for the important relationship between gene dose and expression in Drosophila, but there are at least two general mechanisms that we test here

Methods

Results

Conclusion