Amazing stuff!
"Among many mammals, males and females of the same species look different—a phenomenon called sexual dimorphism. This includes differences in morphology, physiology, and behavior. Sexual dimorphism has long been a topic of interest for evolutionary biologists and ecologists (1). Around 10 years ago, it was acknowledged that disease and drug studies should account for sex, making this topic a focus in biomedical research too (2). Sexual dimorphism is hypothesized to originate in early embryos, but data from prenatal development were lacking. [Researchers] quantify sex bias in gene expression throughout development in six species—five mammals and a bird. They found that sex differences arise around sexual maturity, thus refuting the early-onset hypothesis. They also report that sex-biased gene expression has rapidly evolved, with consequences for understanding evolutionary mechanisms and for the use of preclinical data to make predictions about sex-specific effects of treatments in humans."
From the editor's summary and abstract:
"Because of differences in gene dosage compensation, hormone levels, and other factors, the expression of some genes is known to differ between sexes across sexually reproducing organisms. Rodríguez-Montes et al. looked at gene expression across organs through developmental stages for chicken, mouse, rat, rabbit, opossum, and humans to determine when differences seen in adulthood arise (see the Perspective by Sémon). Although the genes that are found on sex chromosomes or are involved in sex steroid pathways are often sex biased in at least one context, there are few genes with expression that is consistently sex biased across organs, development, or species. These results give insight into the rapid turnover of sex-biased gene expression over evolutionary time.
Structured Abstract
INTRODUCTION
Sexually dimorphic traits are widespread among mammals and emerge during development through sex-specific gene expression programs. We know very little about these programs, including the genes, regulatory networks, and cell types that underlie them. It is also unclear when differences between the sexes emerge during organ development and how sex differences evolve across species.
RATIONALE
To investigate the levels, temporal dynamics, and evolution of sex-biased expression during organ development, we analyzed RNA-sequencing (RNA-seq) time-series data from six species (human, mouse, rat, rabbit, opossum, and chicken) covering the development of five organs (brain, cerebellum, heart, kidney, and liver). Next, we determined the cell-type specificity of sex-biased expression and its conservation across species by analyzing new and existing single-cell RNA-seq datasets. Finally, to understand the mechanisms underlying sex differences in gene expression, we analyzed existing chromatin immunoprecipitation–sequencing datasets to identify the transcription factors responsible for the observed sex-specific gene expression programs.
RESULTS
We found that the levels of sex-biased expression varied substantially across organs and species. Across mammals, sex-biased expression was rare during organ development. In organs with high levels of sex-biased expression, the differences between the sexes only appeared around the time of sexual maturity. Sex-biased expression has evolved rapidly at the gene level, with only a few sex-biased genes conserved among placental mammals. The conserved gene set includes long noncoding RNAs involved in X chromosome inactivation and the X-linked gametologs of ubiquitously expressed Y genes. Unexpectedly, we found that the evolutionary mechanisms underlying this fast evolution differed between organs. In some organs, such as the rabbit heart or the mouse kidney, evolutionarily old genes have quickly evolved sex-biased expression through changes in gene regulation. In other organs, such as the mouse and rat liver, newly evolved genes have driven sex differences, with species differences arising through species-specific genes. Nevertheless, although we found that these genes were species specific, they often belonged to gene families with sex-related functions and sex-biased members in multiple species, indicating cross-species conservation at the level of gene families. We also found that in organs with high levels of sex-biased expression, sex differences were often limited to specific cell types. These cell types were conserved across species in their sexual dimorphism. These results demonstrate that even though sex-biased expression evolves fast at the gene level, it evolves slowly at the level of cell types. Finally, we show that sex-biased expression results from a combinatorial process involving multiple transcription factors and can evolve quickly through the gain or loss of binding sites for a subset of these genes.
CONCLUSION
This study investigated sex differences in gene expression throughout the development of five organs in six species. We found that sex-biased expression varied substantially across organs and species and was often cell-type specific. Sex differences in gene expression were rare during organ development, increasing abruptly only around sexual maturity. Finally, sex-biased expression evolved quickly across species between orthologous genes. However, the cell types responsible for most sex-biased expression were the same across species."
Sex-biased gene expression across mammalian organ development and evolution (no public access)
Sex-biased expression across the development of five organs in six species.
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