Induction and inhibition of Drosophila X chromosome gene expression are both impeded by the dosage compensation complex

Abstract

Sex chromosomes frequently differ from the autosomes in the frequencies of genes with sexually dimorphic or tissue-specific expression. Multiple hypotheses have been put forth to explain the unique gene content of the X chromosome, including selection against male-beneficial X-linked alleles, expression limits imposed by the haploid dosage of the X in males, and interference by the dosage compensation complex (DCC) on expression in males. Here, we investigate these hypotheses by examining differential gene expression in Drosophila melanogaster following several treatments that have widespread transcriptomic effects: bacterial infection, viral infection, and abiotic stress. We found that genes that are induced (up-regulated) by these biotic and abiotic treatments are frequently under-represented on the X chromosome, but so are those that are repressed (down-regulated) following treatment. We further show that whether a gene is bound by the DCC in males can largely explain the paucity of both up- and down-regulated genes on the X chromosome. Specifically, genes that are bound by the DCC, or close to a DCC high-affinity site, are unlikely to be up- or down-regulated after treatment. This relationship, however, could partially be explained by a correlation between differential expression and breadth of expression across tissues. Nonetheless, our results suggest that DCC binding, or the associated chromatin modifications, inhibit both up- and down-regulation of X chromosome gene expression within specific contexts. We propose multiple possible mechanisms of action for the effect, including a role of Males absent on the first (Mof), a component of the DCC, as a dampener of gene expression variance in both males and females. This effect could explain why the Drosophila X chromosome is depauperate in genes with tissue-specific or induced expression, while the mammalian X has an excess of genes with tissue-specific expression.