Disruption of meiotic sex chromosome inactivation by X-autosome translocations in Drosophila melanogaster

In male heterogametic species, the difference in ploidy of the X chromosome between females (XX) and males (XY) has led to the evolution of sex chromosome-specific regulatory mechanisms. In Drosophila melanogaster, expression of the single X chromosome is upregulated in male somatic cells by the well-known process of dosage compensation. In contrast, expression of the X chromosome in the male germline is suppressed by an as yet unknown mechanism that has similarities to mammalian meiotic sex chromosome inactivation. To gain insight into this suppression, we carried out a forward mutagenesis screen for males exhibiting increased expression of a testis-specific, X-linked reporter gene. Two independent mutants were recovered that showed global upregulation of the X chromosome in the male germline and male-specific sterility. Expression of the gene-poor Y chromosome was also upregulated in the mutants. Despite the use of chemical mutagenesis to induce point mutations, both mutants were found to have large, reciprocal translocations between the X chromosome and chromosome arm 3R. Genes on the translocated regions of the X chromosome, encompassing approximately 20 Mb, showed uniform upregulation in testis, which is consistent with a regulatory interaction between the centromeric heterochromatin and the euchromatin. Our observations lend support to classical genetic studies that posited the functional significance of X chromosome suppression in the male germline and its link to male fertility.