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

Abstract

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.

Transposable elements are the primary source of novelty in primate gene regulation

“…This suggests that even modest changes in gene regulation produce significant differences, and confirms that cis-regulatory evolution plays a central role in primate diversification (Davidson 2001(Davidson , 2006Wray 2007;Ho et al 2009;Tsankov et al 2010;Martin et al 2012;Coolon et al 2014;Martin and Reed 2014;Guo et al 2015;Lynch et al 2015;Villar et al 2015;Adachi et al 2016;Landeen et al 2016;Lesch et al 2016;Zhang and Reed 2016).…”

Faster‐X evolution: Theory and evidence from Drosophila

“…In contrast, an autosome spends equal amounts of time in males and females, so that a rare mutation is effectively present only in heterozygotes. For simplicity, full dosage compensation is assumed, implying that hemizygous mutations are equivalent in their effects to homozygous mutations; this is a reasonable assumption for most genes in Drosophila (Ashburner et al, 2005;Georgiev, Chlamydas, & Akhtar, 2011), although recent work suggests that there is a lack of dosage compensation in the male germline (Argyridou, Huylmans, K€ oniger, & Parsch, 2017;Landeen, Muirhead, Wright, Meiklejohn, & Presgraves, 2016;Meiklejohn, Landeen, Cook, Kingan, & Presgraves, 2011).…”

Rapid evolution of female-biased genes among four species of Anopheles malaria mosquitoes

“…This argument is supported by findings that testis-specific genes are, in fact, not underrepresented on the X of Drosophila (Meiklejohn and Presgraves 2012). Instead, testis-specific genes have recruited strong cis-regulatory elements to overcome the transcriptional silencing (Landeen et al 2016). …”

“…Together, these results confirmed the signal previously detected in An. gambiae and suggest that within the male reproductive tissues of Anopheles, likely the testis, X Chromosomes undergo chromosome-wide transcriptional regulation, similarly to Drosophila (Landeen et al 2016). We tested whether such X-specific regulation can explain the underrepresentation of male-biased genes on the X Chromosomes of Anopheles species by simulating the absence of X-regulation in the male reproductive tissues, following the rationale and methods previously used to explore this question using the MozAtlas data in the Meiklejohn and Presgraves (2012) study.…”