Project description:BACKGROUND:Expression patterns between males and females vary in every adult tissue, even in organs with no conspicuous dimorphisms such as the heart. While studies of male and female differences have traditionally focused on the influence of sex hormones, these do not account for all the differences at the molecular and epigenetic levels. We previously reported that a substantial number of genes were differentially expressed in male and female mouse embryonic stem (ES) cells and revealed dose-dependent enhancer activity in response to Prdm14, a key pluripotency factor expressed more highly in female ES cells. In this work, we investigated the role of Prdm14 in establishing sex-specific gene expression networks. We surveyed the sex-specific landscape in early embryogenesis with special reference to cardiac development. We generated sex-specific co-expression networks from mouse ES cells, examined the presence of sex-specific chromatin domains, and analyzed previously published datasets from different developmental time points to characterize how sex-biased gene expression waxes and wanes to evaluate whether sex-biased networks are detectable throughout heart development. RESULTS:We performed ChIP-seq on male and female mouse ES cells to determine differences in chromatin status. Our study reveals sex-biased histone modifications, underscoring the potential for the sex chromosome complement to prime the genome differently in early development with consequences for later expression biases. Upon differentiation of ES cells to cardiac precursors, we found sex-biased expression of key transcription and epigenetic factors, some of which persisted from the undifferentiated state. Using network analyses, we also found that Prdm14 plays a prominent role in regulating a subset of dimorphic expression patterns. To determine whether sex-biased expression is present throughout cardiogenesis, we re-analyzed data from two published studies that sampled the transcriptomes of mouse hearts from 8.5 days post-coitum embryos to neonates and adults. We found sex-biased expression at every stage in heart development, and interestingly, identified a subset of genes that exhibit the same bias across multiple cardiogenic stages. CONCLUSIONS:Overall, our results support the existence of sexually dimorphic gene expression profiles and regulatory networks at every stage of cardiac development, some of which may be established in early embryogenesis and epigenetically perpetuated.

Project description:Stalk-eyed flies (family Diopsidae) are a model system for studying sexual selection due to the elongated and sexually dimorphic eye-stalks found in many species. These flies are of additional interest because their X chromosome is derived largely from an autosomal arm in other flies. To identify candidate genes required for development of dimorphic eyestalks and investigate how sex-biased expression arose on the novel X we compared gene expression between males and females using oligonucleotide microarrays and RNA from developing eyestalk tissue or adult heads in the dimorphic diopsid, Teleopsis dalmanni. Microarray analysis revealed sex-biased expression for 26% of 3,748 genes expressed in eye-antennal imaginal discs and concordant sex-biased expression for 86 genes in adult heads. Overall, 415 female-biased and 482 male-biased genes were associated with dimorphic eyestalk development but not differential expression in the adult head. Functional analysis revealed that male-biased genes are disproportionately associated with growth and mitochondrial function while female-biased genes are associated with cell differentiation and patterning or are novel transcripts. With regard to chromosomal effects, dosage compensation occurs by elevated expression of X-linked genes in males. Genes with female-biased expression were more common on the X and less common on autosomes than expected, while male-biased genes exhibited no chromosomal pattern. Rates of protein evolution were lower for female-biased genes but higher for genes that moved on or off the novel X chromosome. These findings cannot be due to meiotic sex chromosome inactivation or by constraints associated with dosage compensation. Instead, they could be consistent with sexual conflict in which female-biased genes on the novel X act primarily to reduce eyespan in females while other genes increase eyespan in both sexes. Additional information on sex-biased gene expression in other tissues and related sexually monomorphic species could confirm this interpretation.

Project description:Background: Stalk-eyed flies (family Diopsidae) are a model system for studying sexual selection due to the presence of elongated and sexually dimorphic eye-stalks in many species. Recent genomic studies on these flies have revealed a neo-X chromosome and evidence of gene movement onto or off of this X chromosome. To determine if sex linkage and gene movement are related to sexual dimorphism and sexual conflict, we compared gene expression between males and females using oligonucleotide microarrays and RNA from either developing eyestalk tissue or adult heads from a dimorphic species, Teleopsis dalmanni, or from developing eyestalk tissue in a congeneric monomorphic species, T. quinqueguttata. Results: Comparison of gene expression between the sexes for 3,748 genes indicates that dosage compensation is present due to elevated expression of X-linked genes in males. However, sex-biased expression was detected in 26% of the genes present in eye-antennal imaginal discs of larval T. dalmanni. Functional annotation reveals that female-biased genes are associated with transcription, anatomical development and cell communication in the nucleus, while male-biased genes are associated with metabolism and the mitochondria. Comparison of gene expression between experiments identified 140 genes with concordant sex-biased expression in the larval and adult tissues of T. dalmanni and 17 genes with identical sex-biased expression between species. There were only five reversals of sex-biased expression across experiments. In T. dalmanni, male-biased genes are more common on autosomes than on the X while female-biased genes are more common on the X in T. quinqueguttata. Female-biased expression is especially common among genes that moved onto the ancestral X while male-biased expression is more common among genes that moved onto an autosome. Conclusions: Genes with sex-biased expression exhibit different functions in each sex as expected if sexual conflict has influenced their evolution. The strong relationship between sex-biased expression and gene movement found in this study is consistent with resolution of sexual conflict by an RNA- or DNA-mediated process that moves genes between chromosomes. Measurement of gene expression in additional species should provide a more complete picture of how gene expression change occurs over evolutionary time in these extraordinary flies. Two-condition experiment, female vs. male RNA using larval eye discs for two species (Teleopsis dalmanni, Teleopsis quinqueguttata), and adult heads for one species (Teleopsis dalmanni).

Project description:In many species, males and females display differences in their physiology that are not limited to the gonads. Sex differences in adult insects can comprise body size and feeding behaviour, as only female, but not male mosquitoes are blood-feeding in order to produce eggs. This is relevant since the malaria-causing parasite Plasmodium is transmitted by a female mosquito through a previous blood meal from an infected individual. The initiation of sex-specific developmental programs can be often linked to heteromorphic sex chromosomes (XX/XY in Anopheles). In males, the X-linked genes are only present in a single copy. To counteract this hemizygosity, Anopheles, like other species, exhibits dosage compensation (DC). Anopheles DC manifests by upregulation of the single male X ensuring the equal expression of sex-chromosomal genes between males and females. To date, the sex-specific differences at the transcriptome level related to the X/Y chromosomes and DC have been characterized at post-embryonic stages. Their onset during embryogenesis, especially during the early stages where the embryo switches from the maternal to the zygotic transcriptome, is largely uncharacterized to date. Here, we generate a sex-specific transcriptome atlas across Anopheles embryogenesis ending at the first larval stage. Along with the transition from the maternal to the zygotic transcriptome, many transcripts switch isoform, where the 3’ untranslated regions (UTR) of zygotic transcripts are significantly extended compared to their maternal counterpart. We also identify stage- and sex-specific splicing events. Comparing male and female embryos, we identify 120 sexually dimorphic protein coding genes and non-coding RNAs, indicating that sexually dimorphic gene expression is not widespread during embryogenesis. Furthermore, the imbalance of X-linked genes between males and females after zygotic genome activation is corrected shortly after, where the majority of genes exhibit DC around 9 hours of embryogenesis with further fine-tuning later in development. Our atlas provides a framework to explore sex differences in development and evolution and thereby, enables future functional analyses of sex-specific expression patterns and isoform usage.

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The developmental origins of sex-biased expression in cardiac development

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