Sex Chromosome-wide Transcriptional Suppression and Compensatory Cis-Regulatory Evolution Mediate Gene Expression in the Drosophila Male Germline

摘要

The evolution of heteromorphic sex chromosomes has repeatedly resulted in the evolution of sex chromosome-specific forms of regulation, including sex chromosome dosage compensation in the soma and meiotic sex chromosome inactivation in the germline. In the male germline of Drosophila melanogaster , a novel but poorly understood form of sex chromosome-specific transcriptional regulation occurs that is distinct from canonical sex chromosome dosage compensation or meiotic inactivation. Previous work shows that expression of reporter genes driven by testis-specific promoters is considerably lower—approximately 3-fold or more—for transgenes inserted into X chromosome versus autosome locations. Here we characterize this transcriptional suppression of X-linked genes in the male germline and its evolutionary consequences. Using transgenes and transpositions, we show that most endogenous X-linked genes, not just testis-specific ones, are transcriptionally suppressed several-fold specifically in the Drosophila male germline. In wild-type testes, this sex chromosome-wide transcriptional suppression is generally undetectable, being effectively compensated by the gene-by-gene evolutionary recruitment of strong promoters on the X chromosome. We identify and experimentally validate a promoter element sequence motif that is enriched upstream of the transcription start sites of hundreds of testis-expressed genes; evolutionarily conserved across species; associated with strong gene expression levels in testes; and overrepresented on the X chromosome. These findings show that the expression of X-linked genes in the Drosophila testes reflects a balance between chromosome-wide epigenetic transcriptional suppression and long-term compensatory adaptation by sex-linked genes. Our results have broad implications for the evolution of gene expression in the Drosophila male germline and for genome evolution. Expression of sex-linked genes in the Drosophila male germline reflects a balance between an X chromosome-wide transcriptional suppression and long-term, gene-wise evolutionary recruitment of strong, compensatory promoter elements. Author Summary The evolution of different sex chromosomes (e.g., X and Y ) has occurred many times in animals and plants. One consequence of having different chromosome copy numbers between the sexes ( XY males and XX females) is the evolution of sex chromosome-specific regulation, both in the soma (i.e., X chromosome dosage compensation) and in the male germline (i.e., meiotic sex chromosome inactivation). Understanding how the X is regulated in the male germline has implications for gene expression, the evolution of sex chromosome-specific gene content, and speciation. Surprisingly, how the X chromosome is regulated in the Drosophila melanogaster male germline remains unclear. We have characterized X suppression, a novel form of X chromosome transcriptional regulation specific to the Drosophila male germline. Our results reveal that transcription of the X is suppressed 2- to 4-fold for endogenous genes. We show that the X chromosome has evolved strong testis-specific promoters via the gene-by-gene recruitment of sequence elements that counteract transcriptional suppression of the X chromosome. These findings reveal a novel form of X chromosome regulation and lead to a new model for the control of gene expression in the Drosophila male germline.