Stage-Specific Expression Profiling of Drosophila Spermatogenesis Suggests that Meiotic Sex Chromosome Inactivation Drives Genomic Relocation of Testis-Expressed Genes

Abstract

In Drosophila, genes expressed in males tend to accumulate on autosomes and are underrepresented on the X chromosome. In particular, genes expressed in testis have been observed to frequently relocate from the X chromosome to the autosomes. The inactivation of X-linked genes during male meiosis (i.e., meiotic sex chromosome inactivation—MSCI) was first proposed to explain male sterility caused by X-autosomal translocation in Drosophila, and more recently it was suggested that MSCI might provide the conditions under which selection would favor the accumulation of testis-expressed genes on autosomes. In order to investigate the impact of MSCI on Drosophila testis-expressed genes, we performed a global gene expression analysis of the three major phases of D. melanogaster spermatogenesis: mitosis, meiosis, and post-meiosis. First, we found evidence supporting the existence of MSCI by comparing the expression levels of X- and autosome-linked genes, finding the former to be significantly reduced in meiosis. Second, we observed that the paucity of X-linked testis-expressed genes was restricted to those genes highly expressed in meiosis. Third, we found that autosomal genes relocated through retroposition from the X chromosome were more often highly expressed in meiosis in contrast to their X-linked parents. These results suggest MSCI as a general mechanism affecting the evolution of some testis-expressed genes. During the course of Drosophila evolution, genes expressed in males have accumulated on the autosomes. Meiotic sex chromosome X inactivation in males was proposed, among other hypotheses, as a selective force favoring the accumulation of testis-expressed genes on the autosomes. Under such a model, the inactivation of X-linked genes would favor the accumulation of testis-expressed genes in autosomes, wherein these genes would still be expressed. In this study, we observed meiotic expression reduction for X-linked genes in D. melanogaster through a global gene expression analysis in different phases of spermatogenesis, in agreement with MSCI. In order to test the effects of MSCI on the chromosomal distribution of testis-expressed genes, we analyzed their expression pattern throughout spermatogenesis. First, X chromosome underrepresentation was restricted to testis-biased genes over-expressed in meiosis. Second, we observed that the autosomal genes retroposed from the X chromosome more often showed complementary expression in meiosis to their X-linked parents. These results support MSCI in Drosophila, suggesting its mechanistic role in the evolution of testis-expressed genes.