Different But Equal: Settling The Dosage Compensation Debate

In Drosophila, like in humans, male cells have a single Xchromosome, while female cells have two. Researchers have long debatedover how X and autosomal chromosome gene expression is equalizedbetween the sexes (generally regarding two different models, known asthe activation model and the inverse model). These two papers providethe first definitive in vivo evidence in favor of the activation modelof dosage compensation in flies.

The male-specific-lethal (MSL) complex functions as amale-specific regulatory protein complex that controls gene expressionin male fruit fly cells. The activation model proposes that MSLupregulates the transcription of X-linked genes twofold in male cells.The inverse dosage effect model proposes that MSL represses maleautosomal gene expression to balance gene expression.

The Becker and Kuroda labs both utilized RNAi technology toanalyze the effects of decreased MSL expression. Using different, yetcomplementary, experimental systems, both found that MSL downregulationresults in reduced expression of most X-linked genes, while notaffecting autosomal gene expression levels. These results clarify therole of MSL as a specific activator of X-linked gene expression, andthat dosage compensation occurs by a twofold upregulation of the singleX chromosome in male fly cells.

Dr. Becker states that "The clear-cut result we obtainedclarifies this controversial issue at least to our satisfaction. Howthe different components of the male-specific lethal complex contributeto fine-tuning of gene expression in a two-fold range remains aninteresting challenge for future studies."